it 6_aig m. tuberculosis

7/28/2019 It 6_aig m. Tuberculosis

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Tuberculosis

Mycobacterium tuberculosis Acid fast-lipid, wax

Slow growth (nutrient permeability) Resist to detergent and common antibiotics

A leading cause of death by infectious

disease 50% population infected, 3m death/yr Reemergence in 1980 (AIDS, homeless, immigrants)

Diagnose PPD test Chest X-ray Sputum smear (for acid-fast bacilli) Sputum culture


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Stages of disease

Primary infection Asymptomatic to flu-like 3-5% develop TB

Tubercle (granulomatous response) Reactivation (active TB)

Years later, 10% experience

LRT disease (pneumonia) Disseminated miliary TB

Almost everywhere AIDS and antibiotic resistance


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Stages of pathogenesis

Encounter - respiratory droplet

Entry - direct inhalation into LRT (ID=10)

SPREAD - alveoli, but can spreadthroughout body seeding many tissues

Multiplication Grows in phagosome of macrophage

Strict aerobe Very slow in culture (24 hr doubling time)

Evade defenses Inhibits phagolysosomal fusion


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M. tuberculosis


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Diagnosis

Sputum cultureSlow, 13 hour generation time, takes weeks

Acid-fast staining of sputum

Skin testPPD (test previous exposure)

DNA hybridizationPCR (16s rRNA)

Bacteriophage--luciferase gene under M.t. promoterFast detection and test antibiotic susceptibility


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M. tuberculosis

Damage Host response to bacteria (cell-mediated immunity) Glycolipids (Freund adjuvant)

Spread to new hosts Contagious by droplet, resistant to drying

Vaccine - BCG Causes people to become PPD+, not very effective

Infect AIDS Treatment

Unusual set of antibiotics (isoniazid, ethambutol, rifampin) High mutation rate


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Legionnaire's disease/Pontiac Fever

Legionella pneumophila

Gram-negative rodStains irregularlySilver stain

Disease Pontiac Fever - flu-like in anyone (1968)

Legionnaire's disease - pneumonia Primarily in middle aged to older men who

smoke and drink 1976 American Legion Convention in

Philadelphia


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DEMONSTRATION OF THE AGENT OF LEGIONNAIRES` DISEASE


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L. pneumophila


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Stages of pathogenesis Encounter - only from environment by

inhalation

Entry - infects the LRT

Spread - unusual to spread beyond the lungs

Multiplication - fastidious Requires L-cysteine and iron

BCYE-buffered charcoal yeast extract

Evade defenses - intracellular Blocks phagolysosomal fusion

Endoplasmic reticulum-like structure

Damage Inflammation of LRT

Extracellular enzymes?

Spread - Not contagious

Treatment --erythromycin

Vaccine?


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Pseudomonas aeruginosa

Gram negative rod,aerobic

DiseasesLocal infections

CF lungs

Eye

Swimmers ear Urinary tract

Systemic Immunocompromised

Burn patients


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P. aeruginosa

Encounter- air, food, water

Entry- lung, intestine, wound

Spread- any site (motility) Evade defenses-

Multiplication- simple

Damage- toxin and inflammation


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CF lung infection

Defect in ciliary clearance Thick mucus

Ability to grow in mucus

Phenotypic conversion Mucoid(antiphagocytic, biofilm)

Antibiotic resistance

Non-specific Toxins

Exotoxin A, elastase, lipase etc.


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Case #1

A 45 year old female with previousrhinorrhea, pharyngitis, and cough visits herdoctor with a 39oC fever which appearedabruptly after a sudden shaking chill episode.She has chest pain and a productive coughwith rust colored sputum. Auscultationdemonstrates inspiratory rales and "tubular"breath sounds in the right lung. X-ray shows

diffuse lobar consolidation of the right lung.WBC were 52,400/mm3 with 86% neutrophils.


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Case #2

The 16 year old girl complained ofheadache, dry cough, malaise, andtemperature of 38oCfor a couple of

weeks. She denies smoking or drug useand has an unremarkable history, andhas continued to attend school at hermother's insistence. No sputum could

be obtained, and chest X-ray showedvery poorly defined infiltrate inposterior sections.


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Mycoplasma pneumonia

None or minimal productive cough

Serological test rather than culture


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Atypical (walking) pneumoniaMycoplasma pneumonia

Lacks peptidoglycan -lactam resistant

Disease primarily in young adults Encounter - inhalation from human

Entry - restricted to mucosal surface Terminal adhesin protein (P1)

Multiplication - require sterols

Damage Inflammation

Damage and desquamation of ciliated epithelium

Treatments

Erythromycin, doxycycline


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Mycoplasma variable surface antigen(Vsa)

Almost 10% of total protein

C-terminal tandem repeat (up to 60) Recombination phase variation Long Vsa

adherence properties

Short Vsa form biofilm-like aggregates (tower structure)

shield bacteria from host immune responses.


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Model for mycoplasma pathogenesis inthe lungs

it 6_aig m. tuberculosis

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