Download - 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