26.2: Bacterial Diseases of the Nervous System - Biology

26.2: Bacterial Diseases of the Nervous System - Biology

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Learning Objectives

  • Identify the most common bacteria that can cause infections of the nervous system
  • Compare the major characteristics of specific bacterial diseases affecting the nervous system

Bacterial infections that affect the nervous system are serious and can be life-threatening. Fortunately, there are only a few bacterial species commonly associated with neurological infections.

Bacterial Meningitis

Bacterial meningitis is one of the most serious forms of meningitis. Bacteria that cause meningitis often gain access to the CNS through the bloodstream after trauma or as a result of the action of bacterial toxins. Bacteria may also spread from structures in the upper respiratory tract, such as the oropharynx, nasopharynx, sinuses, and middle ear. Patients with head wounds or cochlear implants (an electronic device placed in the inner ear) are also at risk for developing meningitis.

Many of the bacteria that can cause meningitis are commonly found in healthy people. The most common causes of non-neonatal bacterial meningitis are Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. All three of these bacterial pathogens are spread from person to person by respiratory secretions. Each can colonize and cross through the mucous membranes of the oropharynx and nasopharynx, and enter the blood. Once in the blood, these pathogens can disseminate throughout the body and are capable of both establishing an infection and triggering inflammation in any body site, including the meninges (Figure (PageIndex{1})). Without appropriate systemic antibacterial therapy, the case-fatality rate can be as high as 70%, and 20% of those survivors may be left with irreversible nerve damage or tissue destruction, resulting in hearing loss, neurologic disability, or loss of a limb. Mortality rates are much lower (as low as 15%) in populations where appropriate therapeutic drugs and preventive vaccines are available.1

A variety of other bacteria, including Listeria monocytogenes and Escherichia coli, are also capable of causing meningitis. These bacteria cause infections of the arachnoid mater and CSF after spreading through the circulation in blood or by spreading from an infection of the sinuses or nasopharynx. Streptococcus agalactiae, commonly found in the microbiota of the vagina and gastrointestinal tract, can also cause bacterial meningitis in newborns after transmission from the mother either before or during birth.

The profound inflammation caused by these microbes can result in early symptoms that include severe headache, fever, confusion, nausea, vomiting, photophobia, and stiff neck. Systemic inflammatory responses associated with some types of bacterial meningitis can lead to hemorrhaging and purpuric lesions on skin, followed by even more severe conditions that include shock, convulsions, coma, and death—in some cases, in the span of just a few hours.

Diagnosis of bacterial meningitis is best confirmed by analysis of CSF obtained by a lumbar puncture. Abnormal levels of polymorphonuclear neutrophils (PMNs) (> 10 PMNs/mm3), glucose (< 45 mg/dL), and protein (> 45 mg/dL) in the CSF are suggestive of bacterial meningitis.2 Characteristics of specific forms of bacterial meningitis are detailed in the subsections that follow.

Meningococcal Meningitis

Meningococcal meningitis is a serious infection caused by the gram-negative coccus N. meningitidis. In some cases, death can occur within a few hours of the onset of symptoms. Nonfatal cases can result in irreversible nerve damage, resulting in hearing loss and brain damage, or amputation of extremities because of tissue necrosis.

Meningococcal meningitis can infect people of any age, but its prevalence is highest among infants, adolescents, and young adults.3 Meningococcal meningitis was once the most common cause of meningitis epidemics in human populations. This is still the case in a swath of sub-Saharan Africa known as the meningitis belt, but meningococcal meningitis epidemics have become rare in most other regions, thanks to meningococcal vaccines. However, outbreaks can still occur in communities, schools, colleges, prisons, and other populations where people are in close direct contact.

N. meningitidis has a high affinity for mucosal membranes in the oropharynx and nasopharynx. Contact with respiratory secretions containing N. meningitidis is an effective mode of transmission. The pathogenicity of N. meningitidis is enhanced by virulence factors that contribute to the rapid progression of the disease. These include lipooligosaccharide (LOS) endotoxin, type IV pili for attachment to host tissues, and polysaccharide capsules that help the cells avoid phagocytosis and complement-mediated killing. Additional virulence factors include IgA protease(which breaks down IgA antibodies), the invasion factors Opa, Opc, and porin (which facilitate transcellular entry through the blood-brain barrier), iron-uptake factors (which strip heme units from hemoglobin in host cells and use them for growth), and stress proteins that protect bacteria from reactive oxygen molecules.

A unique sign of meningococcal meningitis is the formation of a petechial rash on the skin or mucous membranes, characterized by tiny, red, flat, hemorrhagic lesions. This rash, which appears soon after disease onset, is a response to LOS endotoxin and adherence virulence factors that disrupt the endothelial cells of capillaries and small veins in the skin. The blood vessel disruption triggers the formation of tiny blood clots, causing blood to leak into the surrounding tissue. As the infection progresses, the levels of virulence factors increase, and the hemorrhagic lesions can increase in size as blood continues to leak into tissues. Lesions larger than 1.0 cm usually occur in patients developing shock, as virulence factors cause increased hemorrhage and clot formation. Sepsis, as a result of systemic damage from meningococcal virulence factors, can lead to rapid multiple organ failure, shock, disseminated intravascular coagulation, and death.

Because meningococcoal meningitis progresses so rapidly, a greater variety of clinical specimens are required for the timely detection of N. Required specimens can include blood, CSF, naso- and oropharyngeal swabs, urethral and endocervical swabs, petechial aspirates, and biopsies. Safety protocols for handling and transport of specimens suspected of containing N. meningitidis should always be followed, since cases of fatal meningococcal disease have occurred in healthcare workers exposed to droplets or aerosols from patient specimens. Prompt presumptive diagnosis of meningococcal meningitis can occur when CSF is directly evaluated by Gram stain, revealing extra- and intracellular gram-negative diplococci with a distinctive coffee-bean microscopic morphology associated with PMNs (Figure (PageIndex{2})). Identification can also be made directly from CSF using latex agglutination and immunochromatographic rapid diagnostic tests specific for N. Species identification can also be performed using DNA sequence-based typing schemes for hypervariable outer membrane proteins of N. meningitidis, which has replaced sero(sub)typing.

Meningococcal infections can be treated with antibiotic therapy, and third-generation cephalosporins are most often employed. However, because outcomes can be negative even with treatment, preventive vaccination is the best form of treatment. In 2010, countries in Africa’s meningitis belt began using a new serogroup A meningococcal conjugate vaccine. This program has dramatically reduced the number of cases of meningococcal meningitis by conferring individual and herd immunity.

Twelve different capsular serotypes of N. meningitidis are known to exist. Serotypes A, B, C, W, X, and Y are the most prevalent worldwide. The CDC recommends that children between 11–12 years of age be vaccinated with a single dose of a quadrivalent vaccine that protects against serotypes A, C, W, and Y, with a booster at age 16.4 An additional booster or injections of serogroup B meningococcal vaccine may be given to individuals in high-risk settings (such as epidemic outbreaks on college campuses).


College students living in dorms or communal housing are at increased risk for contracting epidemic meningitis. From 2011 to 2015, there have been at least nine meningococcal outbreaks on college campuses in the United States. These incidents involved a total of 43 students (of whom four died).5 In spite of rapid diagnosis and aggressive antimicrobial treatment, several of the survivors suffered from amputations or serious neurological problems.

Prophylactic vaccination of first-year college students living in dorms is recommended by the CDC, and insurance companies now cover meningococcal vaccination for students in college dorms. Some colleges have mandated vaccination with meningococcal conjugate vaccine for certain students entering college (Figure (PageIndex{3})).

Pneumococcal Meningitis

Pneumococcal meningitis is caused by the encapsulated gram-positive bacterium S. pneumoniae (pneumococcus, also called strep pneumo). This organism is commonly found in the microbiota of the pharynx of 30–70% of young children, depending on the sampling method, while S. pneumoniae can be found in fewer than 5% of healthy adults. Although it is often present without disease symptoms, this microbe can cross the blood-brain barrier in susceptible individuals. In some cases, it may also result in septicemia. Since the introduction of the Hib vaccine, S. pneumoniae has become the leading cause of meningitis in humans aged 2 months through adulthood.

S. pneumoniae can be identified in CSF samples using gram-stained specimens, latex agglutination, and immunochromatographic RDT specific for S. pneumoniae. In gram-stained samples, S. pneumoniae appears as gram-positive, lancet-shaped diplococci (Figure (PageIndex{4})). Identification of S. pneumoniae can also be achieved using cultures of CSF and blood, and at least 93 distinct serotypes can be identified based on the quellung reaction to unique capsular polysaccharides. PCR and RT-PCR assays are also available to confirm identification.

Major virulence factors produced by S. pneumoniae include PI-1 pilin for adherence to host cells (pneumococcal adherence) and virulence factor B (PavB) for attachment to cells of the respiratory tract; choline-binding proteins(cbpA) that bind to epithelial cells and interfere with immune factors IgA and C3; and the cytoplasmic bacterial toxin pneumolysin that triggers an inflammatory response.

With the emergence of drug-resistant strains of S. pneumoniae, pneumococcal meningitis is typically treated with broad-spectrum antibiotics, such as levofloxacin, cefotaxime, penicillin, or other β-lactam antibiotics. The two available pneumococcal vaccines are described in Bacterial Infections of the Respiratory Tract.

Haemophilus influenzae Type b

Meningitis due to H. influenzae serotype b (Hib), an encapsulated pleomorphic gram-negative coccobacilli, is now uncommon in most countries, because of the use of the effective Hib vaccine. Without the use of the Hib vaccine, H. influenzae can be the primary cause of meningitis in children 2 months thru 5 years of age. H. influenzae can be found in the throats of healthy individuals, including infants and young children. By five years of age, most children have developed immunity to this microbe. Infants older than 2 months of age, however, do not produce a sufficient protective antibody response and are susceptible to serious disease. The intracranial pressure caused by this infection leads to a 5% mortality rate and 20% incidence of deafness or brain damage in survivors.6

H. influenzae produces at least 16 different virulence factors, including LOS, which triggers inflammation, and Haemophilus adhesion and penetration factor (Hap), which aids in attachment and invasion into respiratory epithelial cells. The bacterium also has a polysaccharide capsule that helps it avoid phagocytosis, as well as factors such as IgA1 protease and P2 protein that allow it to evade antibodies secreted from mucous membranes. In addition, factors such as hemoglobin-binding protein (Hgp) and transferrin-binding protein (Tbp) acquire iron from hemoglobin and transferrin, respectively, for bacterial growth.

Preliminary diagnosis of H. influenzae infections can be made by direct PCR and a smear of CSF. Stained smears will reveal intracellular and extracellular PMNs with small, pleomorphic, gram-negative coccobacilli or filamentous forms that are characteristic of H. influenzae. Initial confirmation of this genus can be based on its fastidious growth on chocolate agar. Identification is confirmed with requirements for exogenous biochemical growth cofactors NAD and heme (by MALDI-TOF), latex agglutination, and RT-PCR.

Meningitis caused by H. influenzae is usually treated with doxycycline, fluoroquinolones, second- and third-generation cephalosporins, and carbapenems. The best means of preventing H. influenza infection is with the use of the Hib polysaccharide conjugate vaccine. It is recommended that all children receive this vaccine at 2, 4, and 6 months of age, with a final booster dose at 12 to 15 months of age.7

Neonatal Meningitis

S. agalactiae, Group B streptococcus (GBS), is an encapsulated gram-positive bacterium that is the most common cause of neonatal meningitis, a term that refers to meningitis occurring in babies up to 3 months of age.8 S. agalactiae can also cause meningitis in people of all ages and can be found in the urogenital and gastrointestinal microbiota of about 10–30% of humans.

Neonatal infection occurs as either early onset or late-onset disease. Early onset disease is defined as occurring in infants up to 7 days old. The infant initially becomes infected by S. agalactiae during childbirth, when the bacteria may be transferred from the mother’s vagina. Incidence of early onset neonatal meningitis can be greatly reduced by giving intravenous antibiotics to the mother during labor.

Late-onset neonatal meningitis occurs in infants between 1 week and 3 months of age. Infants born to mothers with S. agalactiae in the urogenital tract have a higher risk of late-onset menigitis, but late-onset infections can be transmitted from sources other than the mother; often, the source of infection is unknown. Infants who are born prematurely (before 37 weeks of pregnancy) or to mothers who develop a fever also have a greater risk of contracting late-onset neonatal meningitis.

Signs and symptoms of early onset disease include temperature instability, apnea (cessation of breathing), bradycardia(slow heart rate), hypotension, difficulty feeding, irritability, and limpness. When asleep, the baby may be difficult to wake up. Symptoms of late-onset disease are more likely to include seizures, bulging fontanel (soft spot), stiff neck, hemiparesis (weakness on one side of the body), and opisthotonos (rigid body with arched back and head thrown backward).

S. agalactiae produces at least 12 virulence factors that include FbsA that attaches to host cell surface proteins, PI-1 pilithat promotes the invasion of human endothelial cells, a polysaccharide capsule that prevents the activation of the alternative complement pathway and inhibits phagocytosis, and the toxin CAMP factor, which forms pores in host cell membranes and binds to IgG and IgM antibodies.

Diagnosis of neonatal meningitis is often, but not uniformly, confirmed by positive results from cultures of CSF or blood. Tests include routine culture, antigen detection by enzyme immunoassay, serotyping of different capsule types, PCR, and RT-PCR. It is typically treated with β-lactam antibiotics such as intravenous penicillin or ampicillin plus gentamicin. Even with treatment, roughly 10% mortality is seen in infected neonates.9

Exercise (PageIndex{1})

  1. Which groups are most vulnerable to each of the bacterial meningitis diseases?
  2. For which of the bacterial meningitis diseases are there vaccines presently available?
  3. Which organism can cause epidemic meningitis?

Clostridium-Associated Diseases

Species in the genus Clostridium are gram-positive, endospore-forming rods that are obligate anaerobes. Endospores of Clostridium spp. are widespread in nature, commonly found in soil, water, feces, sewage, and marine sediments. Clostridium spp. produce more types of protein exotoxins than any other bacterial genus, including two exotoxins with protease activity that are the most potent known biological toxins: botulinum neurotoxin (BoNT) and tetanus neurotoxin (TeNT). These two toxins have lethal doses of 0.2–10 ng per kg body weight.

BoNT can be produced by unique strains of C. butyricum, and C. baratii; however, it is primarily associated with C. botulinum and the condition of botulism. TeNT, which causes tetanus, is only produced by C. tetani. These powerful neural exotoxins are the primary virulence factors for these pathogens. The mode of action for these toxins was described in Virulence Factors of Bacterial and Viral Pathogens and illustrated in [link].

Diagnosis of tetanus or botulism typically involves bioassays that detect the presence of BoNT and TeNT in fecal specimens, blood (serum), or suspect foods. In addition, both C. botulinum and C. tetani can be isolated and cultured using commercially available media for anaerobes. ELISA and RT-PCR tests are also available.


Tetanus is a noncommunicable disease characterized by uncontrollable muscle spasms (contractions) caused by the action of TeNT. It generally occurs when C. tetani infects a wound and produces TeNT, which rapidly binds to neural tissue, resulting in an intoxication (poisoning) of neurons. Depending on the site and extent of infection, cases of tetanus can be described as localized, cephalic, or generalized. Generalized tetanus that occurs in a newborn is called neonatal tetanus.

Localized tetanus occurs when TeNT only affects the muscle groups close to the injury site. There is no CNS involvement, and the symptoms are usually mild, with localized muscle spasms caused by a dysfunction in the surrounding neurons. Individuals with partial immunity—especially previously vaccinated individuals who neglect to get the recommended booster shots—are most likely to develop localized tetanus as a result of C. tetani infecting a puncture wound.

Cephalic tetanus is a rare, localized form of tetanus generally associated with wounds on the head or face. In rare cases, it has occurred in cases of otitis media (middle ear infection). Cephalic tetanus often results in patients seeing double images, because of the spasms affecting the muscles that control eye movement.

Both localized and cephalic tetanus may progress to generalized tetanus—a much more serious condition—if TeNT is able to spread further into body tissues. In generalized tetanus, TeNT enters neurons of the PNS. From there, TeNT travels from the site of the wound, usually on an extremity of the body, retrograde (back up) to inhibitory neurons in the CNS. There, it prevents the release of gamma aminobutyric acid (GABA), the neurotransmitter responsible for muscle relaxation. The resulting muscle spasms often first occur in the jaw muscles, leading to the characteristic symptom of lockjaw (inability to open the mouth). As the toxin progressively continues to block neurotransmitter release, other muscles become involved, resulting in uncontrollable, sudden muscle spasms that are powerful enough to cause tendons to rupture and bones to fracture. Spasms in the muscles in the neck, back, and legs may cause the body to form a rigid, stiff arch, a posture called opisthotonos (Figure (PageIndex{5})). Spasms in the larynx, diaphragm, and muscles of the chest restrict the patient’s ability to swallow and breathe, eventually leading to death by asphyxiation (insufficient supply of oxygen).

Neonatal tetanus typically occurs when the stump of the umbilical cord is contaminated with spores of C. tetani after delivery. Although this condition is rare in the United States, neonatal tetanus is a major cause of infant mortality in countries that lack maternal immunization for tetanus and where birth often occurs in unsanitary conditions. At the end of the first week of life, infected infants become irritable, feed poorly, and develop rigidity with spasms. Neonatal tetanus has a very poor prognosis with a mortality rate of 70%–100%.10

Treatment for patients with tetanus includes assisted breathing through the use of a ventilator, wound debridement, fluid balance, and antibiotic therapy with metronidazole or penicillin to halt the growth of C. In addition, patients are treated with TeNT antitoxin, preferably in the form of human immunoglobulin to neutralize nonfixed toxin and benzodiazepines to enhance the effect of GABA for muscle relaxation and anxiety.

A tetanus toxoid (TT) vaccine is available for protection and prevention of tetanus. It is the T component of vaccines such as DTaP, Tdap, and Td. The CDC recommends children receive doses of the DTaP vaccine at 2, 4, 6, and 15–18 months of age and another at 4–6 years of age. One dose of Td is recommended for adolescents and adults as a TT booster every 10 years.11


Botulism is a rare but frequently fatal illness caused by intoxication by BoNT. It can occur either as the result of an infection by C. botulinum, in which case the bacteria produce BoNT in vivo, or as the result of a direct introduction of BoNT into tissues.

Infection and production of BoNT in vivo can result in wound botulism, infant botulism, and adult intestinal toxemia. Wound botulism typically occurs when C. botulinum is introduced directly into a wound after a traumatic injury, deep puncture wound, or injection site. Infant botulism, which occurs in infants younger than 1 year of age, and adult intestinal toxemia, which occurs in immunocompromised adults, results from ingesting C. botulinum endospores in food. The endospores germinate in the body, resulting in the production of BoNT in the intestinal tract.

Intoxications occur when BoNT is produced outside the body and then introduced directly into the body through food (foodborne botulism), air (inhalation botulism), or a clinical procedure (iatrogenic botulism). Foodborne botulism, the most common of these forms, occurs when BoNT is produced in contaminated food and then ingested along with the food (recall Case in Point: A Streak of Bad Potluck). Inhalation botulism is rare because BoNT is unstable as an aerosol and does not occur in nature; however, it can be produced in the laboratory and was used (unsuccessfully) as a bioweapon by terrorists in Japan in the 1990s. A few cases of accidental inhalation botulism have also occurred. Iatrogenic botulism is also rare; it is associated with injections of BoNT used for cosmetic purposes (see Micro Connections: Medicinal Uses of Botulinum Toxin).

When BoNT enters the bloodstream in the gastrointestinal tract, wound, or lungs, it is transferred to the neuromuscular junctions of motor neurons where it binds irreversibly to presynaptic membranes and prevents the release of acetylcholine from the presynaptic terminal of motor neurons into the neuromuscular junction. The consequence of preventing acetylcholine release is the loss of muscle activity, leading to muscle relaxation and eventually paralysis.

If BoNT is absorbed through the gastrointestinal tract, early symptoms of botulism include blurred vision, drooping eyelids, difficulty swallowing, abdominal cramps, nausea, vomiting, constipation, or possibly diarrhea. This is followed by progressive flaccid paralysis, a gradual weakening and loss of control over the muscles. A patient’s experience can be particularly terrifying, because hearing remains normal, consciousness is not lost, and he or she is fully aware of the progression of his or her condition. In infants, notable signs of botulism include weak cry, decreased ability to suckle, and hypotonia (limpness of head or body). Eventually, botulism ends in death from respiratory failure caused by the progressive paralysis of the muscles of the upper airway, diaphragm, and chest.

Botulism is treated with an antitoxin specific for BoNT. If administered in time, the antitoxin stops the progression of paralysis but does not reverse it. Once the antitoxin has been administered, the patient will slowly regain neurological function, but this may take several weeks or months, depending on the severity of the case. During recovery, patients generally must remain hospitalized and receive breathing assistance through a ventilator.

Exercise (PageIndex{2})

  1. How frequently should the tetanus vaccination be updated in adults?
  2. What are the most common causes of botulism?
  3. Why is botulism not treated with an antibiotic?


Although it is the most toxic biological material known to man, botulinum toxin is often intentionally injected into people to treat other conditions. Type A botulinum toxin is used cosmetically to reduce wrinkles. The injection of minute quantities of this toxin into the face causes the relaxation of facial muscles, thereby giving the skin a smoother appearance. Eyelid twitching and crossed eyes can also be treated with botulinum toxin injections. Other uses of this toxin include the treatment of hyperhidrosis (excessive sweating). In fact, botulinum toxin can be used to moderate the effects of several other apparently nonmicrobial diseases involving inappropriate nerve function. Such diseases include cerebral palsy, multiple sclerosis, and Parkinson’s disease. Each of these diseases is characterized by a loss of control over muscle contractions; treatment with botulinum toxin serves to relax contracted muscles.


Listeria monocytogenes is a nonencapsulated, nonsporulating, gram-positive rod and a foodborne pathogen that causes listeriosis. At-risk groups include pregnant women, neonates, the elderly, and the immunocompromised (recall the Clinical Focus case studies in Microbial Growth and Microbial Mechanisms of Pathogenicity). Listeriosis leads to meningitis in about 20% of cases, particularly neonates and patients over the age of 60. The CDC identifies listeriosis as the third leading cause of death due to foodborne illness, with overall mortality rates reaching 16%.12 In pregnant women, listeriosis can cause also cause spontaneous abortion in pregnant women because of the pathogen’s unique ability to cross the placenta.

L. monocytogenes is generally introduced into food items by contamination with soil or animal manure used as fertilizer. Foods commonly associated with listeriosis include fresh fruits and vegetables, frozen vegetables, processed meats, soft cheeses, and raw milk.13 Unlike most other foodborne pathogens, Listeria is able to grow at temperatures between 0 °C and 50 °C, and can therefore continue to grow, even in refrigerated foods.

Ingestion of contaminated food leads initially to infection of the gastrointestinal tract. However, L. monocytogenes produces several unique virulence factors that allow it to cross the intestinal barrier and spread to other body systems. Surface proteins called internalins (InlA and InlB) help L. monocytogenes invade nonphagocytic cells and tissues, penetrating the intestinal wall and becoming disseminating through the circulatory and lymphatic systems. Internalins also enable L. monocytogenes to breach other important barriers, including the blood-brain barrier and the placenta. Within tissues, L. monocytogenes uses other proteins called listeriolysin O and ActA to facilitate intercellular movement, allowing the infection to spread from cell to cell (Figure (PageIndex{6})).

L. monocytogenes is usually identified by cultivation of samples from a normally sterile site (e.g., blood or CSF). Recovery of viable organisms can be enhanced using cold enrichment by incubating samples in a broth at 4 °C for a week or more. Distinguishing types and subtypes of L. monocytogenes—an important step for diagnosis and epidemiology—is typically done using pulsed-field gel electrophoresis. Identification can also be achieved using chemiluminescence DNA probe assays and MALDI-TOF.

Treatment for listeriosis involves antibiotic therapy, most commonly with ampicillin and gentamicin. There is no vaccine available.

Exercise (PageIndex{3})

How does Listeria enter the nervous system?

Hansen’s Disease (Leprosy)

Hansen’s disease (also known as leprosy) is caused by a long, thin, filamentous rod-shaped bacterium Mycobacterium leprae, an obligate intracellular pathogen. M. leprae is classified as gram-positive bacteria, but it is best visualized microscopically with an acid-fast stain and is generally referred to as an acid-fast bacterium. Hansen’s disease affects the PNS, leading to permanent damage and loss of appendages or other body parts.

Hansen’s disease is communicable but not highly contagious; approximately 95% of the human population cannot be easily infected because they have a natural immunity to M. leprae. Person-to-person transmission occurs by inhalation into nasal mucosa or prolonged and repeated contact with infected skin. Armadillos, one of only five mammals susceptible to Hansen’s disease, have also been implicated in transmission of some cases.14

In the human body, M. leprae grows best at the cooler temperatures found in peripheral tissues like the nose, toes, fingers, and ears. Some of the virulence factors that contribute to M. leprae’s pathogenicity are located on the capsule and cell wall of the bacterium. These virulence factors enable it to bind to and invade Schwann cells, resulting in progressive demyelination that gradually destroys neurons of the PNS. The loss of neuronal function leads to hypoesthesia (numbness) in infected lesions. leprae is readily phagocytized by macrophages but is able to survive within macrophages in part by neutralizing reactive oxygen species produced in the oxidative burst of the phagolysosome. Like L. monocytogenes, M. leprae also can move directly between macrophages to avoid clearance by immune factors.

The extent of the disease is related to the immune response of the patient. Initial symptoms may not appear for as long as 2 to 5 years after infection. These often begin with small, blanched, numb areas of the skin. In most individuals, these will resolve spontaneously, but some cases may progress to a more serious form of the disease. Tuberculoid (paucibacillary) Hansen’s disease is marked by the presence of relatively few (three or less) flat, blanched skin lesions with small nodules at the edges and few bacteria present in the lesion. Although these lesions can persist for years or decades, the bacteria are held in check by an effective immune response including cell-mediated cytotoxicity. Individuals who are unable to contain the infection may later develop lepromatous (multibacillary) Hansen’s disease. This is a progressive form of the disease characterized by nodules filled with acid-fast bacilli and macrophages. Impaired function of infected Schwann cells leads to peripheral nerve damage, resulting in sensory loss that leads to ulcers, deformities, and fractures. Damage to the ulnar nerve (in the wrist) by M. leprae is one of the most common causes of crippling of the hand. In some cases, chronic tissue damage can ultimately lead to loss of fingers or toes. When mucosal tissues are also involved, disfiguring lesions of the nose and face can also occur (Figure (PageIndex{7})).

Hansen’s disease is diagnosed on the basis of clinical signs and symptoms of the disease, and confirmed by the presence of acid-fast bacilli on skin smears or in skin biopsy specimens (Figure (PageIndex{7})). leprae does not grow in vitro on any known laboratory media, but it can be identified by culturing in vivo in the footpads of laboratory mice or armadillos. Where needed, PCR and genotyping of M. leprae DNA in infected human tissue may be performed for diagnosis and epidemiology.

Hansen’s disease responds well to treatment and, if diagnosed and treated early, does not cause disability. In the United States, most patients with Hansen’s disease are treated in ambulatory care clinics in major cities by the National Hansen’s Disease program, the only institution in the United States exclusively devoted to Hansen’s disease. Since 1995, WHO has made multidrug therapy for Hansen’s disease available free of charge to all patients worldwide. As a result, global prevalence of Hansen’s disease has declined from about 5.2 million cases in 1985 to roughly 176,000 in 2014.15 Multidrug therapy consists of dapsone and rifampicin for all patients and a third drug, clofazimin, for patients with multibacillary disease.

Currently, there is no universally accepted vaccine for Hansen’s disease. India and Brazil use a tuberculosis vaccineagainst Hansen’s disease because both diseases are caused by species of Mycobacterium. The effectiveness of this method is questionable, however, since it appears that the vaccine works in some populations but not in others.

Exercise (PageIndex{4})

  1. What prevents the progression from tuberculoid to lepromatus leprosy?
  2. Why does Hansen’s disease typically affect the nerves of the extremities?


Disfiguring, deadly diseases like leprosy have historically been stigmatized in many cultures. Before leprosy was understood, victims were often isolated in leper colonies, a practice mentioned frequently in ancient texts, including the Bible. But leper colonies are not just an artifact of the ancient world. In Hawaii, a leper colony established in the late nineteenth century persisted until the mid-twentieth century, its residents forced to live in deplorable conditions.16 Although leprosy is a communicable disease, it is not considered contagious (easily communicable), and it certainly does not pose enough of a threat to justify the permanent isolation of its victims. Today, we reserve the practices of isolation and quarantine to patients with more dangerous diseases, such as Ebola or multiple-drug-resistant bacteria like Mycobacterium tuberculosis and Staphylococcus aureus. The ethical argument for this practice is that isolating infected patients is necessary to prevent the transmission and spread of highly contagious diseases—even when it goes against the wishes of the patient.

Of course, it is much easier to justify the practice of temporary, clinical quarantining than permanent social segregation, as occurred in leper colonies. In the 1980s, there were calls by some groups to establish camps for people infected with AIDS. Although this idea was never actually implemented, it begs the question—where do we draw the line? Are permanent isolation camps or colonies ever medically or socially justifiable? Suppose there were an outbreak of a fatal, contagious disease for which there is no treatment. Would it be justifiable to impose social isolation on those afflicted with the disease? How would we balance the rights of the infected with the risk they pose to others? To what extent should society expect individuals to put their own health at risk for the sake of treating others humanely?


Despite the formidable defenses protecting the nervous system, a number of bacterial pathogens are known to cause serious infections of the CNS or PNS. Unfortunately, these infections are often serious and life threatening. Figure (PageIndex{8}) summarizes some important infections of the nervous system.

Key Concepts and Summary

  • Bacterial meningitis can be caused by several species of encapsulated bacteria, including Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, and Streptococcus agalactiae (group B streptococci). influenzae
affects primarily young children and neonates, N. meningitidis is the only communicable pathogen and mostly affects children and young adults, S. pneumoniae affects mostly young children, and S. agalactiae affects newborns during or shortly after birth.
  • Symptoms of bacterial meningitis include fever, neck stiffness, headache, confusion, convulsions, coma, and death.
  • Diagnosis of bacterial meningitis is made through observations and culture of organisms in CSF. Bacterial meningitis is treated with antibiotics. influenzae and N. meningitidis have vaccines available.
  • Clostridium species cause neurological diseases, including botulism and tetanus, by producing potent neurotoxins that interfere with neurotransmitter release. The PNS is typically affected. Treatment of Clostridium infection is effective only through early diagnosis with administration of antibiotics to control the infection and antitoxins to neutralize the endotoxin before they enter cells.
  • Listeria monocytogenes is a foodborne pathogen that can infect the CNS, causing meningitis. The infection can be spread through the placenta to a fetus. Diagnosis is through culture of blood or CSF. Treatment is with antibiotics and there is no vaccine.
  • Hansen’s disease (leprosy) is caused by the intracellular parasite Mycobacterium leprae. Infections cause demylenation of neurons, resulting in decreased sensation in peripheral appendages and body sites. Treatment is with multi-drug antibiotic therapy, and there is no universally recognized vaccine.
  • Footnotes

    1. 1 Thigpen, Michael C., Cynthia G. Whitney, Nancy E. Messonnier, Elizabeth R. Zell, Ruth Lynfield, James L. Hadler, Lee H. Harrison et al., “Bacterial Meningitis in the United States, 1998–2007,” New England Journal of Medicine 364, no. 21 (2011): 2016-25.
    2. 2 Popovic, T., et al. World Health Organization, “Laboratory Manual for the Diagnosis of Meningitis Caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenza,” 1999.
    3. 3 US Centers for Disease Control and Prevention, “Meningococcal Disease,” August 5, 2015. Accessed June 28, 2015.
    4. 4 US Centers for Disease Control and Prevention, “Recommended Immunization Schedule for Persons Aged 0 Through 18 Years, United States, 2016,” February 1, 2016. Accessed on June 28, 2016.
    5. 5 National Meningitis Association, “Serogroup B Meningococcal Disease Outbreaks on U.S. College Campuses,” 2016. Accessed June 28, 2016.
    6. 6 United States Department of Health and Human Services, “Hib (Haemophilus Influenzae Type B),” Accessed June 28, 2016.
    7. 7 US Centers for Disease Control and Prevention, “Meningococcal Disease, Disease Trends,” 2015. Accessed September 13, 2016.
    8. 8 Thigpen, Michael C., Cynthia G. 21 (2011): 2016-25.
    9. 9 Thigpen, Michael C., Cynthia G. 21 (2011): 2016-25; Heath, Paul T., Gail Balfour, Abbie M. Weisner, Androulla Efstratiou, Theresa L. Lamagni, Helen Tighe, Liam AF O’Connell et al., “Group B Streptococcal Disease in UK and Irish Infants Younger than 90 Days,” The Lancet 363, no. 9405 (2004): 292-4.
    10. 10 UNFPA, UNICEF WHO, “Maternal and Neonatal Tetanus Elimination by 2005,” 2000.
    11. 11 US Centers for Disease Control and Prevention, “Tetanus Vaccination,” 2013. Accessed June 29, 2016.
    12. 12 Scallan, Elaine, Robert M. Hoekstra, Frederick J. Angulo, Robert V. Tauxe, Marc-Alain Widdowson, Sharon L. Roy, Jeffery L. Jones, and Patricia M. Griffin, “Foodborne Illness Acquired in the United States—Major Pathogens,” Emerging Infectious Diseases 17, no. 1 (2011): 7-15.
    13. 13 US Centers for Disease Control and Prevention, “Listeria Outbreaks,” 2016.
    14. 14 Sharma, Rahul, Pushpendra Singh, W. J. Loughry, J. Mitchell Lockhart, W. Barry Inman, Malcolm S. Duthie, Maria T. Pena et al., “Zoonotic Leprosy in the Southeastern United States,” Emerging Infectious Diseases 21, no. 12 (2015): 2127-34.
    15. 15 World Health Organization, “Leprosy Fact Sheet,” 2016.
    16. 16 National Park Service, “A Brief History of Kalaupapa,” Accessed February 2, 2016.


    • Nina Parker, (Shenandoah University), Mark Schneegurt (Wichita State University), Anh-Hue Thi Tu (Georgia Southwestern State University), Philip Lister (Central New Mexico Community College), and Brian M. Forster (Saint Joseph’s University) with many contributing authors. Original content via Openstax (CC BY 4.0; Access for free at

    Veterinary Microbiology and Microbial Disease, 2nd Edition

    Tables, boxes and flow diagrams provide information in an easily assimilated format. This edition contains new chapters on molecular diagnostics and on infectious conditions of the skin, cardiovascular system, urinary tract and musculoskeletal system. Many new colour diagrams are incorporated into this edition and each chapter has been updated.

    Key features of this edition:

    • Twelve new chapters included
    • Numerous new illustrations
    • Each chapter has been updated
    • Completely re-designed in full colour
    • Fulfils the needs of veterinary students and academics in veterinary microbiology
    • Companion website with figures from the book as Powerpoints for viewing or downloading by chapter:

    Veterinary Microbiology and Microbial Disease remains indispensable for all those studying and teaching this essential component of the veterinary curriculum.

    Interactive resources for schools

    Plasma cell membrane

    The membrane which forms the boundary between the cytoplasm of a cell and the medium surrounding it. It is selectively permeable to ions and organic molecules and controls the movemennt of substances in and out of cells.

    Endocrine system

    The system of hormones (endocrines) that bring about chemical coordination of the body



    Protein molecules attached to cells that only bind to specific molecules with a particular structure

    The structure of the nervous system

    The need for nervous coordination

    A single celled organism carries out all the functions of life within its plasma cell membrane. However once organisms become multicellular they need to coordinate what happens in all of their different cells.

    As multicellular organisms get bigger and bigger, cells differentiate and form tissues and organs which carry out specific functions. It is important that the different body systems work together. Animals have the biggest problem because they need to move around to find food and mates. A nervous system gives them a coordination system that works fast.

    The simple nerve net of a sea anemone allows it to coordinate the movements of its tentacles so it can capture prey
    (Photo: Anthony Short)

    The human nervous system

    The human body is made up of around 10 billion cells which all have to work together to keep you alive. People need to move about, avoid danger, find food, water and mates, control their body temperature and coordinate the activities of all the main body systems (for example the digestive system and circulatory system). This coordination is brought about by the nervous system and the endocrine system. The nervous system provides rapid coordination using electrical impulses which travel around the body fast – from about 1-120 metres per second.

    In humans the nervous system is made up of the following parts:

    • Receptors – these are specialised cells which are sensitive to changes in the environment (stimuli). Receptor cells are adapted to respond to different stimuli such as light or sound. Lots of receptor cells are often found together in sense organs for example the eye contains light sensitive cells the nose contains cells which are sensitive to taste.
    • Neurones – these are cells which are adapted to carry information in the form of electrical impulses. They have long extensions which mean impulses can travel all around the body. Sensory neurones carry information from sensory receptors to the central nervous system. Motor neurones carry information from the central nervous system to the effector organs. These are the muscles and glands which bring about changes in response to stimuli.

    Click on the diagram to reveal the labels.

    A nerve is a bundle of neurones. Sensory nerves contain only sensory neurones, motor nerves contain only motor neurones and mixed nerves carry both.

    • The central nervous system (CNS) – this is made up of the brain and the spinal cord. Impulses from sensory neurones feed into the CNS. Here the sensory information is processed. The CNS coordinates the response to the incoming information and then sends out impulses along the motor neurones. As a result the body responds to the original stimulus.

    The way the nervous system works to control the responses of your body can be summed up as:

    receptor → sensory neurone → coordinator (CNS) → motor neurone → effector

    How the nervous system works to coordinate a conscious response to a stimulus.

    Question 1

    a) Which type of neurone carries impulses from the CNS to the muscles and glands of the body?

    b) Which two structures make up the human central nervous system?

    c) Summarise the way that the nervous system coordinates and controls your body

    receptor → sensory neurone → coordinator (CNS) → motor neurone → effector


    We thank D. Eisenberg, H. LeVine, A. Aguzzi, J. Collinge, R. Rosen, Y. Eisele, A. Mehta, M. Gearing, J. Manson, M. Neumann, and the members of our laboratories for critical discussions and comments. The help of H. Braak with Fig. 1, and the help of S. Eberle with the manuscript and figures is gratefully acknowledged. This work was supported by grants from the Competence Network on Degenerative Dementias (BMBF-01GI0705), ALZKULT (BMBF-031A198A), NGFN2 (BMBF-01GS08131), and anonymous foundations (to M.J.), and by National Institutes of Health grants R21AG040589, P51RR165, P51OD11132, and the CART Foundation (to L.C.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    Bosque PJ, Tyler KL. Prions and prion disease of the central nervous system (transmissible neurodegenerative diseases). In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Philadelphia, PA: Elsevier 2020:chap 179.

    Tee BL, Geschwind MD. Prion diseases. In: Jankovic J, Mazziotta JC, Pomeroy SL, Newman NJ, eds. Bradley and Daroff's Neurology in Clinical Practice. 8th ed. Philadelphia, PA: Elsevier 2022:chap 94.

    Definition of Botulism

    Botulism refers to a clinical condition during which the neurotoxin of Clostridium botulinum paralyzes the involuntary muscles by inhibiting the motor nerve endings from synthesizing acetylcholine. Clostridium botulinum commonly releases neurotoxin (Botulinum neurotoxin), which accumulates in the small intestine. A botulinum neurotoxin mainly affects the nervous system and paralyzes the involuntary muscles of the body. Botulism can occur in both humans and animals.

    Causes of Botulism

    Botulism is caused by a neurotoxin produced by Clostridium botulinum. Neurotoxin is an exotoxin, which affects the nervous system. Botulism is a clinical condition, paralyzes the involuntary muscles and further spreads to the respiratory system and the heart. Based on serological specificity, neurotoxins are categorized into the following seven serological types:

    1. Type A: It is a type of human botulism, which is very common in the western regions of the United States.
    2. Type B: It is also a type of human botulism that occurs frequently, and it is less toxic than type-A.
    3. Type-C: It is not a type of human botulism and causes botulism in cattle, fowls etc.
    4. Type-D: It mostly causes forage poisoning of cattle in South African countries.
    5. Type-E: This type of neurotoxin is obtained chiefly from fish and fish products. Type-E is very toxic to humans.
    6. Type-F: It was first isolated in Denmark and is a type of human botulism.
    7. Type-G: This has been recently isolated from the soil in Argentina, and it is not a type of human botulism.

    Food Sources

    The spores of Clostridium botulinum sporulate to produce a neurotoxin, which can be present in the following food sources:

    • Canned meat
    • Canned fish
    • Honey syrup
    • Sweet corn
    • Fermented beans
    • Other low acid foods

    Spores of Clostridium botulinum generally grows in favourable conditions like:

    1. Low acid
    2. Anaerobic environment
    3. Low sugar
    4. Low salt
    5. And low temperature.

    Types of Botulism

    There are three forms of botulism caused by Clostridium botulinum:

    Foodborne botulism: It spreads by eating food contaminated with the spores produced by the Clostridium botulinum. Foodborne botulism develops after the consumption of unprocessed, undercooked, canned and unrefrigerated food.

    • Symptoms include:
      • Blurred vision
      • Difficulty in swallowing
      • Muscle weakness
      • Dry mouth
      • Nausea
      • Vomiting
      • Abdominal cramps
      • Paralysis etc.

      Wound botulism: It spreads when the spores of the bacteria (Clostridium botulinum) enters the body through a cut or any mechanical injuries. The spores of Clostridium botulinum sporulate to produce neurotoxin within the wound. The risk factors include people who are addicted to drugs like heroin.

      • Symptoms include:
        • Slurred speaking
        • Double vision
        • Drooping eyelids
        • Paralysis etc.

        Infant botulism: It spreads by the ingestion of the Clostridium botulinum spores that grow in the infant’s intestinal tract of age limit between 2-8 months. Infant botulism develops after the consumption of honey syrup.

        • Symptoms include:
          • Constipation
          • Floppy movements
          • Irritation
          • Drooping eyelids
          • Paralysis etc.

          In addition to this, there are some other types also that occur very rarely. Adult botulism is rarely seen, in which the spores of the Clostridium botulinum colonize in the digestive tract of adults. Iatrogenic botulism is very lethal, which occurs by an overdose of botulinum neurotoxin or botox.

          Types of Neurotoxin Effects

          Botulinum neurotoxin can produce the following type of effects:

          1. Local effect: The local effects of Clostridium botulinum includes the following symptoms:
            • Blurred vision
            • Muscle weakness
            • Dry mouth
            • Reduced gag reflex etc.
          2. Immunological effect: It occurs by the administration of equine antitoxin.
          3. Metabolic effect: It is characterized by a symptom (respiratory acidosis).

          Symptoms of Botulism disease

          A neurotoxin produced by Clostridium botulinum can affect the cardiovascular, respiratory and central nervous system etc.

          1. Effect on the cardiovascular system: Botulinum neurotoxin blocks the automatic nervous system and leads to cause tachycardia and hypertension.
          2. On respiratory system: A neurotoxin paralyzes the respiratory muscle and results in ventilatory failure, and ultimately leads to death.
          3. Effect on the nervous system:
            • Central nervous system: Botulinum neurotoxin paralyzes the cranial nerves and causes symptoms like:
              • Blurred vision
              • Diplopia
              • Dysphonia
              • Dysarthria
              • Dysphagia etc.
            • Peripheral nervous system: After paralyzing cranial nerves, botulinum neurotoxin causes symmetrical descending paralysis, affecting the respiratory muscles.
            • Automatic nervous system: Botulinum neurotoxin blocks the autonomic cholinergic junctions and causes the following symptoms:
              • Blurred vision
              • Orthostatic hypotension
              • Constipation
              • Urinary retention etc.
          4. Skeletal and smooth muscles: Botulinum neurotoxin affects the skeletal and smooth muscles by causing gallbladder dysfunction and necrotic fasciitis.
          5. Effect on Gastrointestinal system: A neurotoxin shows the gastrointestinal symptoms after 18-36 hours of incubation, and the symptoms include:
            • Nausea
            • Vomiting
            • Abdominal cramps
            • Diarrhoea
            • It sometimes leads to cause constipation, gastric dilatation and paralytic ileus.
          6. Neurotoxin does not directly affect the hepatic system (liver) and the urinary bladder.


          A neurotoxin produced by the Clostridium botulinum causes botulism by following a given pathogenic cycle:

          1. First, neurotoxin enters the bloodstream through the ingestion of the bacterial spores or from the mucosal surface.
          2. Botulinum neurotoxin blocks the nerve terminal ends.
          3. Then, it binds to the neuronal membrane.
          4. After that, a neurotoxin enters the cytoplasm of the axon terminal.
          5. Then, botulinum neurotoxin blocks the excitatory synaptic transmission and results in interference with the synthesis of neurotransmitter “Acetylcholine”.
          6. Finally, it causes flaccid paralysis, as the nervous system cannot function without the action of acetylcholine. Acetylcholine plays an essential role in producing nerve impulse and the process of muscle contraction.


          There are many cases of botulism, and if it remains untreated, then the mortality rate reaches about 50-60%. Treated patients may also concur with botulism, with a mortality rate of about 3-5%. The diagnosis or treatment of botulism should be made early otherwise, it can cause major outbreaks.


          There are a few first aid measures that can control the transmission of the disease to some extent.

          Foodborne botulism: To prevent its transmission

          • Avoid eating canned food
          • Properly wash and boil the vegetables before eating.
          • Trash the canned food that is bulging or leaking.
          • Avoid eating foods that are added with preservatives.
          • Avoid eating undercooked food.

          Wound botulism: To prevent its transmission

          • Properly sanitize the wounded area.
          • Maintain proper body hygiene.
          • Do not let the wound open to the air, as the spores of Clostridium botulinum can penetrate inside the cells through any cuts or injuries.

          Infant botulism: To prevent infant botulism, keep the body hygienic and don’t give corn or honey syrup to the infants.


          The early symptoms of botulism can be treated by the oral administration of polyvalent antitoxin. Enemas are found effective in the removal of the unabsorbed toxin.


          Diagnosis of botulism involves the following tests:

          Mouse inoculation test: It is the most reliable and popular method to detect the presence of C.botulinum. Mouse inoculation test involves two series of tests. In one experiment, a patient’s stool is injected into the peritoneal cavity of mice. And, in the second test, an equal amount of the patient’s stool plus multivalent antitoxin is injected into the other mice.

          If the mice live, by the injection of antitoxin and stool sample and die by the infusion of an untreated serum sample, then it gives a positive result for botulism. Mouse inoculation test detects the presence of particularly A, B and E serotypes of C. botulinum.

          Physical tests: It includes tests like brain scan, spinal fluid examination, nerve conduction test (electromyography).

          Genetic Manipulation of the Nervous System

          Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most diverse and rapidly advancing fields in the life sciences.
          Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas.
          The recent development of Gene Therapy procedures which allow specific genes to be delivered to human patients who lack functional copies of them is of major therapeutic importance. In addition such gene delivery methods can be used in other organisms to define the function of particular genes. These studies are of particular interest in the nervous system where there are many incurable diseases like Alzheimer's and Parkinson's diseases which may benefit from therapies of this kind. Unfortunately gene delivery methods for use in the nervous system have lagged behind those in other systems due to the fact that the methods developed in other systems are often not applicable to cells like neurons which do not divide. This book discusses a wide range of methods which have now been developed to overcome these problems and allow safe and efficient delivery of particular genes to the brain. Methods discussed include virological methods, physical methods (such as liposomes) and the transplantation of genetically modified cells. In a single volume therefore this book provides a complete view of these methods and indicates how they can be applied to the development of therapies for treating previously incurable neurological disorders.

          Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most diverse and rapidly advancing fields in the life sciences.
          Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas.
          The recent development of Gene Therapy procedures which allow specific genes to be delivered to human patients who lack functional copies of them is of major therapeutic importance. In addition such gene delivery methods can be used in other organisms to define the function of particular genes. These studies are of particular interest in the nervous system where there are many incurable diseases like Alzheimer's and Parkinson's diseases which may benefit from therapies of this kind. Unfortunately gene delivery methods for use in the nervous system have lagged behind those in other systems due to the fact that the methods developed in other systems are often not applicable to cells like neurons which do not divide. This book discusses a wide range of methods which have now been developed to overcome these problems and allow safe and efficient delivery of particular genes to the brain. Methods discussed include virological methods, physical methods (such as liposomes) and the transplantation of genetically modified cells. In a single volume therefore this book provides a complete view of these methods and indicates how they can be applied to the development of therapies for treating previously incurable neurological disorders.

          26.2: Bacterial Diseases of the Nervous System - Biology

          All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited.

          Feature Papers represent the most advanced research with significant potential for high impact in the field. Feature Papers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer review prior to publication.

          The Feature Paper can be either an original research article, a substantial novel research study that often involves several techniques or approaches, or a comprehensive review paper with concise and precise updates on the latest progress in the field that systematically reviews the most exciting advances in scientific literature. This type of paper provides an outlook on future directions of research or possible applications.

          Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

          This work was supported by grants from the National Natural Science Foundation of China (nos. 81573471) the Key Laboratory of Virology of Guangzhou, China (201705030003) Key Projects of Biological Industry Science & Technology of Guangzhou China (grant no. 201504291048224) Guangzhou Industry, University and Research Collaborative Innovation Major Project (nos. 201604020178 and 201704030087) and The Public Service Platform of South China Sea for Rɭ Marine Biomedicine Resources, Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China.

          The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

          How herpesvirus invades nervous system

          Northwestern Medicine scientists have identified a component of the herpesvirus that "hijacks" machinery inside human cells, allowing the virus to rapidly and successfully invade the nervous system upon initial exposure.

          Led by Gregory Smith, associate professor in immunology and microbiology at Northwestern University Feinberg School of Medicine, researchers found that viral protein 1-2, or VP1/2, allows the herpesvirus to interact with cellular motors, known as dynein. Once the protein has overtaken this motor, the virus can speed along intercellular highways, or microtubules, to move unobstructed from the tips of nerves in skin to the nuclei of neurons within the nervous system.

          This is the first time researchers have shown a viral protein directly engaging and subverting the cellular motor most other viruses passively hitch a ride into the nervous system.

          "This protein not only grabs the wheel, it steps on the gas," says Smith. "Overtaking the cellular motor to invade the nervous system is a complicated accomplishment that most viruses are incapable of achieving. Yet the herpesvirus uses one protein, no others required, to transport its genetic information over long distances without stopping."

          Herpesvirus is widespread in humans and affects more than 90 percent of adults in the United States. It is associated with several types of recurring diseases, including cold sores, genital herpes, chicken pox, and shingles. The virus can live dormant in humans for a lifetime, and most infected people do not know they are disease carriers. The virus can occasionally turn deadly, resulting in encephalitis in some.

          Until now, scientists knew that herpesviruses travel quickly to reach neurons located deep inside the body, but the mechanism by which they advance remained a mystery.

          Smith's team conducted a variety of experiments with VP1/2 to demonstrate its important role in transporting the virus, including artificial activation and genetic mutation of the protein. The team studied the herpesvirus in animals, and also in human and animal cells in culture under high-resolution microscopy. In one experiment, scientists mutated the virus with a slower form of the protein dyed red, and raced it against a healthy virus dyed green. They observed that the healthy virus outran the mutated version down nerves to the neuron body to insert DNA and establish infection.

          "Remarkably, this viral protein can be artificially activated, and in these conditions it zips around within cells in the absence of any virus. It is striking to watch," Smith says.

          He says that understanding how the viruses move within people, especially from the skin to the nervous system, can help better prevent the virus from spreading.

          Additionally, Smith says, "By learning how the virus infects our nervous system, we can mimic this process to treat unrelated neurologic diseases. Even now, laboratories are working on how to use herpesviruses to deliver genes into the nervous system and kill cancer cells."

          Smith's team will next work to better understand how the protein functions. He notes that many researchers use viruses to learn how neurons are connected to the brain.

          "Some of our mutants will advance brain mapping studies by resolving these connections more clearly than was previously possible," he says.

          Watch the video: Dr. Parkers Microbiology Chapter 22-Disease of the Nervous System (May 2022).