LECTURE - Mycobacterium tuberculosis Flashcards
TB was on its way to being controlled in the 80s so what happened in the 80s?
- immigration
- crowding and substance abuse leading to HIV = in homeless shelters and prisons
what are NTM?
- also known as mycobacteria other than tuberculosis (MOTT) or ‘atypical mycobacteria’
- normally inhabit the environment, but some can cause tuberculosis-like disease in humans
- HIV-AIDS HAS GREATLY increased awareness of disease caused by these organisms
preferred medium to grow NTM
Lowenstein-Jensen medium
Runyon Classification
useful distinctions observed among NTM species based on three key features:
- growth RATE on LJ medium (slow growers >7 days; rapid 3-7 days)
- optimal growth temp (30-32 C, 35-37 C, 42 C)
- photoreactivity =
> photochromogens: produce pigment on exposure to light
> scotochromogens produce pigment in the light or dark
> nonchromogenic produce no pigments (buff colour)
slow growers
Mycobacterium tuberculosis
Mycobacterium avium complex
Mycobacterium leprae
- acid-fast Fite stain for this anaerobic rod
- does NOT grow in vitro; grow in footpads of mice or armadillos
- AKA Hansen’s disease (leprosy); rare here but still a challenge worldwide
how is leprosy transmitted?
droplets from nose and mouth of untreated patients with severe disease BUT not highly infectious
- left untreated = cause nerve damage = muscle weakness, atrophy, and permanent disabilities
treatment of leprosy
MDT = multidrug therapy
leprosy can occur in two polar forms:
- tuberculoid (TT)
- lepromatous (LL)
with 3 intermediate (borderline) forms, depending no state of cell-mediated immunity (CMI)
WHO only makes a distinction for leprosy between these two
- PB paucibacillary = no bacilli present
- MB multibacillary = bacilli present
TB causes death in ___% of untreated cases
50%
W strain of TB
extremely drug resistant!!! (XDR-TB)
one of the top ten causes of death worldwide
tB
worldwide, TB is the ___th leading cause of death and the _____ leading infectious killer (after COVI-19 and above HIV/AIDS)
13th; secind leading
T or F. TB is not curable
F! it is!
TB characteristics
- acid-fast aerobic gram pos rod ; much extra lipid and an outer, mycomembrane, akin to that of gram negs
- very slow growth
- spread by aerosols
- fever, cough (often w blood sputum); irreversible lung damage; can disseminate throughout body
- skin test pos confirms exposure (1% of those exposed develop TB IF healthy!) (40% if HIV-positive)
steps in migration of M. tb across the alveolar barrier
- adheres to, invades, and replicates in alveolar epithelial cells
- penetrates the BM and endothelial cells
- exits the ECs to enter circulation
- infects extra-pulmonary EC to establish latent TB infection (LTBI) in EP sites
- ‘Trojan Horse’ mechanism by which M. tb crosses the barrier via infected alveolar macrophages
KEY to beating TB
efficient production of CD4+ and CD8+ cells and the activation of macrophages that can kill M. tb
antibodies = minimal effect
latency in TB
- ability of organisms to survive in body for many decades; hypotheses:
1. organism stops replacing in a quasi-sporelike state; sigF is known to regulate spore formation in Streptomyces sp.
2. organism still metabolically active but barely; antibiotics reduce likelihood of reactivation of TB so bacteria must be metabolizing at least a little
presumptive diagnosis of TB using this stain
Ziehl-Neelsen (acid-fast)
- reveals M. tb as pink acid-fast bacilli in sputum
secretion system unique to mycobacteria
type VII (ESX) secretion system
t kill M. tb, special antibiotics are required…
- exceptions are rifampin and streptomycin
- Ethambutol appears to be, and isoniazid is, an inhibitor of the mycolic acid synthesis
- mechanism of pyrazinamide appears to be disruption of membrane transport and energetics
resistance to anti-TB drugs
- resistance to rifampin and isoniazid occurs at high frequency, so using both drugs together reduces this chance; most common therapy for TB!
- many TB drugs = daily pills for six months+ and it’s hard to comply= resistance! (ep. if drugs make you nauseated)
- high mutation rates as well
targets for new TB drugs
- isocitrate lyase in the glyoxylate cycle of M.tb metabolism that is linked to latency
- Or enzymes that make up the antigen 85 complex = transferring mycolic acids onto trehalose residues in cell walls
how to diagnose TB?
- sputum and detection of FB (presumptive)
- skin test (Mantoux); uses purified protein derivative to detect prior exposure based on previously primed CD4+ T cells
- radiography (chest x-ray)
- WHO recommends rapid test based on PCR (detects TB and resistance to rifampin); Xpert MTB/RIF test; nucleic acid amplification test
1 virulence characteristic of M. tb
ability to grow in resting macrophages (mediated by ESX-1 genes)
how does TB trigger a destructive immune response
- muramyl dipeptide stimulates cytokine secretion
- TNNF-alpha is produced in response to various cell wall components and triggers lung damage; Abs to TNF-alpha can prevent this
- release of lysosomal components of macs and PMNs
host susceptibility to TB depends on: (4)
- dose of organisms
- exposure time to inoculum
- health of individual
- genetic factors of host and of bacterium
treatment for leprosy today
- early to avert disability!
- MDT (multidrug therapy) = dapsone, rifampicin, and clofazimine ; kills pathogen and cures patient
T or F. immunological manifestations can everse upon antibiotic therapy (Leprosy)
T! have to keep immune system dampened so that CMI doesn’t go nuts with MB leprosy and MDT
