Bacterial pathogens Neisseria meningitidis, Helicobacter pylori, Mycobacterium tuberculosis

Overview
N. meningitidis H. pylori M. tuberculosis
Morphology Growth and metabolic characteristics Pathogenicity factors Diseases Diagnostic
Latex agglutination Spot test Culture PCR Immue response

Therapy Threats

Neisseria meningitidis

Neisseria meningitidis
Gram-negative aerobic diplococci Capsule
Serotypes A, B, C, W-135, Y US: C, Y, and W-135 (infants: B)

10% of people are healthy nasopharyngeal carriers

N. meningitidis: Pathogenicity Factors

Pili Opa protein IgA2 proteases Capsule LPS release Molecular mimickry of host structures

N. meningitidis: Diseases
Bacterial meningitis
Acute onset High fever Headache and stiff neck Followed by nausea and vomiting May progress to convulsions and coma 10%-14% of cases are fatal Patients who recover 11%-19% have permanent hearing loss, mental retardation

Meninogococcal sepsis
Waterhouse Friderichsen syndrome (lead to various organ failure
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Waterhouse-Friderichsen Syndrome
N. meningitidis sepsis disseminated intravascular coagulation and multiorgan failure Septic Shock and bleeding into adrenal gland Petechial skin lesions (bleeding into skin) Death within 12 48 hours

N. meningitidis: Diagnostic
Gram stain Latex agglutination Culture

N. meningitidis: Therapy
Prophylaxis with rifampin, ciprofloxacin, or ceftriaxone for household and other close contacts

Threats by N. meningitidis
Massive epidemic outbreaks in sub-Saharan Africa in the 1990's Emergence since 1995 of serogroups Y, W-135 and X Risk groups
Infants and young children Refugees household contacts of case patients military recruits college freshmen who live in dormitories microbiologists who work with isolates of N. meningitidis

Patients without spleens or with terminal complement component deficiencies

Helicobacter pylori

Helicobacter pylori
Gram-negative rod Curved Microaerophilic Epsilon-proteobacteria Specialty growth media

H. pylori: Pathogenicity Factors

Urease
Increases gastric pH
Structure and activity of VacA

Vacuolating cytotoxin (VacA) Helicobacter pylori neutrophil activating protein (HP-NAP) TNFE inducing protein (TipE)

H. pylori: Diseases
Colonizes ~ 66 % of the world population
Source: seawater?

Gastric ulcer Dyspepsia Carcinoma

Host genetic factors Bacterial virulence factors Environmental and lifestyle factors

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H. pylori: Diagnostic
Serology: detection of antibodies Breath test
13C- or 14C-labeled urea drink H. pylori metabolizes the urea rapidly Labeled carbon can then be measured as *CO

Endoscopy
Bed-side urease test Biopsy
Culture (difficult)

H. pylori: Therapy
Clarithromycin and amoxycillin plus a proton pump inhibitor 10 days to 2 weeks

Threats by H. pylori
Increased numbers of newly diagnosed esophageal adenocarcinomas despite (or because of?) the eradication of H. pylori

Mycobacterium tuberculosis

M. tuberculosis
Acid fast rods Lipid-rich cell wall
Mycolic acids

Loewenstein Jensen agar

Eggs Potatoes Malachit green

Slow growth
Up to 6 weeks
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M. tuberculosis: Pathogenicity Factors

Lipid-rich cell wall
Mycolic acids

Resistant to host defense Intracellular survival in macrophages Requires a T-cell mediated immune response for infection control/eradication Granuloma formation

The Course of TB Infection and Disease

Airborne Infection 90 %
Latent TB No symptoms Not sick Cannot spread disease Chest X Ray and sputum are normal

10 % TB Disease
Symptoms Can sp[read infection Positive skin test Possible abnormal chest X ray Positive sputum smear or culture Dissemination

AIDS increases susceptibility Untreated: Severe illness, Death

Reactivation (secondary) TB

M. tuberculosis: Diseases
General Symptoms
Feelings of sickness or weakness Weight loss Fever Night sweats

Lung tuberculosis
Coughing Chest pain Hemoptysis

Extrapulmonary
Depends on localization

Lung Tuberculosis

Extrapulmonary Tuberculosis

M. tuberculosis: Diagnostic
History Physical exam Mantoux Skin test (tuberculin test with purified protein drivative) QuantiFERON-TB Gold Test Chest radiograph Sputum smear Culture

Principle of the Tuberculin Test

QuantiFERON-TB Gold Test

Measure IFNK production by patient peripheral blood leukocytes in response to M. tuberculosis antigens. Rapid T cell response only in primed individuals

Interpretation of Tuberculin and QuantiFERON

Positive = previous contact with M. tuberculosis Positive DOES NOT mean TB disease

M. tuberculosis: Therapy
Isoniazid (INH) Rifampin (RIF) Ethambutol Pyrazinamide

At least 2 in combination (INH + RIF) Prolonged time (at least 6 months)

DOTS
Direct observational therapy short course

Threats by M. tuberculosis
1/3 of world population is infected 5 10 % will develop active TB However: In 2006, a total of 13,767 tuberculosis (TB) cases (4.6 per 100,000 population) in the US
3.2% decline from 2005

Co-infection with HIV Multidrug resistant Tb Extremely drug-resistant Tb

Extremely Drug-Resistant M. tuberculosis

XDR TB Resistant to almost all drugs used to treat TB, including the two best first-line drugs: isoniazid and rifampin Resistant to the best second-line medications: fluoroquinolones And at least one of three injectable drugs (i.e., amikacin, kanamycin, or capreomycin). 49 cases of XDR TB have been reported between 1993 and 2006

Take Home Message (1)

N. meningitis is an extracellular pathogen that resists phagocytosis and can induce a major LPS mediated inflammatory response with rapid fatal outcome. Bordetella pertussis exhibits numerous pathogenic factors representing adhesisn, cytotoxins and Type III secretion apparatus. There is a mismatch between vaccine strains and current isolates possibly accounting for the re-emergence of the formerly early childhood disease among adolescents.

Take Home Message (2)

Two thirds of the world population is infected H. pylori, which is the only bacterium that has been proven to cause cancer. However, host genetic and environmental factors as well as age of infection with H. pylori determine whether cancer develops. One third of the world population is infected with M. tuberculosis but only 10% develop active disease. The lipid rich cell wall and slow growth contribute to resistance to host defense and difficulties in antibiotic treatment. The emergence of extremely drug resistant tuberculosis strains poses a great threat to the public.

Resources
The Microbial Challenge, by Krasner, ASM Press, Washington DC, 2002. Brock Biology of Microorganisms, by Madigan and Martinko, Pearson Prentice Hall, Upper Saddle River, NJ, 11th ed, 2006. Microbiology: An Introduction, by Tortora, Funke and Case; Pearson Prentice Hall; 9th ed, 2007. Immunobiology, by Janeway,, Travers, Walport, and Shlomchik, Garland Science, 6th ed, 2005. Nicole Guiso (2005) Is Bordetella pertussis Changing . Microbe 71 231-234. Malak Kotb Genetics of Susceptibility to Infectious Diseases Volume 70, Number 10, 2004 / ASM News Y 457-463 Bernard Dixon MicrobeLibrary Article: Microbe 2005 htttp://www.cdc.gov/ulcer/keytocure.htm#whatis Layke JC, Lopez PP. Esophageal cancer: a review and update. Am Fam Physician. 2006 Jun 15;73(12):2187-94. http://dermatlas.med.jhmi.edu/derm/resultNoCache.cfm