Mycobacterium Flashcards

1
Q

what kind of bacteria does this describe?
- thin, rod shaped
- obligate aerobes
- non-motile
- tough cell wall and envelope with high lipid content
- acid fast
- slow growing

A

mycobacterium: has mycomembrane with mycolic acid (long lipid chain) —> makes wall highly impermeable, hardy —> high transmissibility and resistance to antibiotics, acid fast staining

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2
Q

describe the clinical effect/importance of the mycomembrane of mycobacterium

A

mycobacterium: has mycomembrane with mycolic acid (long lipid chain) —> makes wall highly impermeable, hardy —> high transmissibility and resistance to antibiotics, acid fast staining

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3
Q

what are mycobacterial-specific features of the cell wall? (4)

A
  1. acyl lipids
  2. mycolate (mycolic acid): long lipid chain, contributes to impermeability and antibiotic resistance
  3. arabinogalactan: biopolymer of arabinose + galactose monosaccharides
  4. LAM (lipoarabinomannan)
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4
Q

what kind of bacteria has the following in its cell wall?

  1. acyl lipids
  2. mycolate
  3. arabinogalactan
  4. LAM (lipoarabinomannan)
A

mycobacterium

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5
Q

what is different about the peptidoglycan found on the cell walls of mycobacterium?

A

peptidoglycan contains N-glucolylmuramic acid instead of N-acetylmuramic acid

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6
Q

explain why mycobacterium is considered “acid fast”

A

the cell wall and outer mycomembrane is so tough that it absorbs dye too well, and even acid alcohol cannot decolorize it

thus, they are “acid fast”

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7
Q

what 2 staining techniques can be used for mycobacterium? describe them

A
  1. Ziehl-Neelsen (ZN) acid-fast staining: Carbol Fuchsin + acid-alcohol decolorize + methylene blue counterstain = red mycobacterium on blue background
  2. fluorochrome stain: Auramine O-Rhodamine + acid alcohol + potassium permanganate (removes autofluorescence) = yellow mycobacterium on background (more sensitive but less specific)
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8
Q

what are 2 ways to divide mycobacterium, of which there are 100+ species?

A
  1. Mtb (Mycobacterium tuberculosis) complex: all cause TB, so species level ID is not clinically necessary (but useful for epidemiology), all form non-pigmented colonies
    [M. tuberculosis, M. bovis, M. bovis BCG, M. africanum, M. microti, M. canettii]
  2. NTMs (non-tuberculous mycobacteria): ubiquitous, aka environmental or atypical mycobacteria, classified by pigmentation with/without light
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9
Q

M. tuberculosis, M. bovis, M. bovis BCG, M. africanum, M. microti, M. canettii all belong to what group?

A

Mtb (mycobacterium tuberculosis) complex: mycobacteria that all cause TB and form non-pigmented colonies

ID is not necessary for clinical purposes (all cause TB), but good for epidemiology

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10
Q

how is TB transmitted?

A

via mycobacterium tuberculosis (MTB complex) in respiratory droplets —> bacilli travel to alveoli

some patients are never infectious, others infectious for months

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11
Q

describe the pathogenesis of TB

A

mycobacterium tuberculosis (MTB complex) inhaled via respiratory droplet, bacilli travel to alveoli

tubercle bacilli multiple in alveolar macrophages —> early logarithmic growth prior to immune response

2-8 weeks: cell mediated immunity develops, activated macrophages form granuloma —> LTBI (latent TB infection), Mtb in dormancy

*recall latent TB is delayed/Type IV hypersensitivity

becoming immunocompromised (HIV, age) may allow TB escape and dissemination —> active disease, miliary TB

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12
Q

how does a lung TB infection look histologically?

A

granulomas with Langerhan’s giant cells (foamy macrophages)

bacilli can persist in granulomas for a very long time

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13
Q

how can delayed (type IV) hypersensitivity of LTBI (latent TB infection) be demonstrated with a diagnostic value? (2)

describe these tests

A
  1. interferon-gamma release assay (IGRA): measure immune reactivity based on IFNy release (measure whole blood, whole blood + Mtb peptides, whole blood + mitogen)
  2. tuberculin skin test (TST): aka Mantoux test, inject Mtb extract or purified protein (PPD) —> ring of induration is measured (48-72h later)

[remember that Type IV hypersensitivity is Th1 mediated]

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14
Q

describe how tuberculin skin test (TST) is read and interpreted

A

aka Mantoux test: inject Mtb extract or purified protein (PPD) —> specific T cells recruited, which produce IFNy and activate macrophages —> ring of induration is measured (48-72h later)

smaller diagnostic values are considered positive for high-risk populations (sliding scale interpretation)

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15
Q

describe how the IGRA TB test works

A

IFNy release assay: measure IFNy released from blood T-lymphocytes that have been infected with Mtb, using 3 measurements of IFNy:

  1. whole blood alone: baseline
  2. whole blood + Mtb peptides: measures stimulated IFNy in response to recombinant, specific Mtb antigen (NOT cross-reactive with BCG as skin test can be)
  3. whole blood + non-specific activator of WBC (mitogen): demonstrates WBCs are present and capable of secreting IFNy
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16
Q

what is the major advantage of IFNy release assay over skin test for TB diagnosing? how are they typically used for high vs low risk patients?

A

TST can cause cross-reactivity to other mycobacteria, giving false (+)

while IGRA measures stimulated IFNy release in response to recombinant, specific Mtb antigens

*for high risk patients, a second diagnostic test should be performed even if initial test is neg. - do not want to miss early diagnosis (increase sensitivity) - diagnosis made with single positive test

*for low risk patients, a confirmatory test is used following an initial positive result (ensure specificity) - LTBI ruled out with single neg. test

17
Q

active TB may represent reinfection, reactivation, or progressing primary infection

in this case, tubercle bacilli escape granuloma and disseminate

what is this termed?

A

miliary TB: TB infected lymph node erodes a vessel wall and tubercle bacilli spread via blood

on x-ray, see diffuse miliary pattern (“millet seeds”) throughout lung

18
Q

which of these is true of active TB disease but NOT LTBI?
a. may spread TB mycobacterium to others
b. usually (+) TST or IGRA
c. needs treatment

A

person with latent TB (LTBI) CANNOT spread TB mycobacterium to others, also have normal chest x-ray

*also note that persons with active infection are symptomatic while persons with LTBI are asymptotic

19
Q

tissue injury following TB infection is a consequence of…

A

immune response (rather than specific toxins and virulence factors)

host destroys itself to control intracellular bacterial growth

caseous necrosis and cavity formation

20
Q

what kind of necrosis does TB cause

A

TB is most common cause of caseous necrosis (“cheese like”)

necrotic cellular debris surrounded by zone of suppurative inflammation

21
Q

describe how non-tuberculous mycobacteria (NTMs) are classified

(aka environmental or atypical mycobacteria)

A

Runyon classification (4 groups):

  1. photochromogens: pigmentation only in light - M. kansasii, M. marinum
  2. Scotochromogens: pigmentation with/without light - M. gordonae, M. xenopi, M. scrofulaceum
  3. nonphotochromogens: M. avium complex (MAC), M. ulcerans
  4. rapid growers: M. abscessus, M. chelonae, M. fortuitum
22
Q

what kind of bacteria (including classification) is M. kansasii, and what kind of illness does it cause?

A

NTM: non-tuberculous mycobacteria, Runyon classification is photochromogen (Group 1 - pigmentation only in light)

causes chronic pulmonary infections involving upper lobes of lungs (resembles MTB clinically)

*dissemination is rare except in AIDS

23
Q

where does M. kansasii (NTM, photochromogen) come from, and how can it be identified?

A

tap water is major reservoir

slow growing, responds quickly to antimicrobial therapy

ID with DNA probe

24
Q

which bacteria species does this describe?
- photochromogen
- tap water is major reservoir
- causes chronic pulmonary infection
- slow growing, and dissemination is rare except in AIDS

A

M. kansasii: non-tuberculous mycobacteria (NTM), responds quickly to antimicrobial therapy

remember photochromogen (Group I Runyon classification) means it only pigments in light

25
Q

what kind of bacteria (including classification) is M. marinum, and what kind of illness does it cause?

A

non-tuberculous mycobacteria (NTM), photochromogen (Group 1 Runyon, pigmentation in light), grows slowly

causes cutaneous infection associated with exposure to salt/freshwater - “swimming pool granuloma” or “fish tank granuloma”

26
Q

what bacteria species does this describe?
- most common in southern coastal states
- photochromogenic
- causes “swimming pool” or “fish tank” granuloma

A

M. marinum: NTM, Group 1 Runyon (photochromogen - pigmentation in light)

causes cutaneous infection associated with exposure to salt/freshwater

grows slowly

27
Q

what kind of bacteria (including classification) is M. gordonae?

A

non-tuberculous mycobacteria (NTM), scotochromogen (Group 2 Runyon, pigmentation with/without light)

most common non-pathogenic NTM - no treatment required

found in soil/water, colonizes respiratory tract

DNA probe for ID

28
Q

what kind of bacteria (including classification) is M. xenopi? what kind of disease does it cause?

A

non-tuberculous mycobacteria (NTM), scotochromogen (Group 2 Runyon, pigmentation with/without light)

causes chronic pulmonary disease in adults with underlying lung disease (COPD)

29
Q

what kind of bacteria are those in the M. avium complex (MAC)?

A

MAC: M. avium, M. intracellular, M. paratuberculosis

non-tuberculous mycobacterium (NTMs), nonphotochromogens (Group 3 Runyon)

most commonly isolated mycobacterium spp. (species)

slow growing, ID with DNA probe

30
Q

what kind of bacteria are M. abscessus, M. fortuitum, and M. chelonae?

A

rapid-growing mycobacteria (RGM), Group 5 of non-tuberculous mycobacteria (NTM) - growth in <7 days (fast for mycobacteria)

often healthcare facility-acquired (considered preventable) - post-traumatic/surgical/injection wound infections —> causes pulmonary infections with abscesses that are difficult to treat

31
Q

describe the nature of infection by Mycobacterium leprae

A
  • cannot be cultivated in vitro (armadillo animal model)
  • spread person to person, likely via nasal secretions
  • long incubation (could be years)
  • either lepromatous (widespread lesion with high bacterial loading) or tuberculoid (limited lesions with low bacterial loading)
32
Q

what 3 kinds of testing need to be performed for mycobacterium, and what is the timeline for each?

A
  1. smearing/staining: acid fast or fluorochrome staining (hours)
  2. NAAT/PCR (hours)
  3. cultivation: identification and susceptibility testing, to guide clinical treatment (weeks)
33
Q

what does “cording” with an acid-fast stain indicate, and what causes it?

A

cording is characteristic of Mycobacterium tuberculosis (MTB)

due to cording factor trehalose dimycolate - considered virulence factor because it can kill phagocytes (anti-cord antibodies are protective)

34
Q

what is the CDC guideline regarding culturing mycobacterium?

A

both solid and liquid media inoculated (liquid media reduces turn-around time)

incubation for 8 weeks (mycobacterium are slow-growing)