mycobacteria Flashcards
tb history
About 1/4 of the world’s population is estimated to be infected with
Mycobacterium tuberculosis, but are not ill with it.
According to the WHO, in 2022 tuberculosis infected an estimated
10.6 million people and killed about 1.3 million people, including
167,000 people with HIV/AIDS. Incidence is highest in India,
China, Indonesia, the Phillippines Nigeria, Bangladesh, and
Pakistan
In 2019, there were 206,000 new cases of multidrug- or rifampin-
resistance
tb risk
HIV infection: 18 times more likely to develop active TB
Undernutrition: 3 times more risk
Alcohol use disorder: 3.3 times more likely
Tobacco use: 1.6 times more likely
Poverty
Poor housing
May proceed to
a generalized
Infection: “miliary”
tuberculosis
Tb and HIV
TB is a leading killer of HIV-positive people causing ¼ of all HIV-
related deaths
People living with HIV are 26 to 31 times more likely to develop
active TB disease than people without HIV
Up to 13 million people in the US are infected with M. tuberculosis
without displaying symptoms
1 in 10 of these individuals will develop active TB at some time in
their lives
tb stain
Mycobacteria stained with the Ziehl-Neelsen stain
Mycobacteria are termed “Acid-fast bacteria”
Physiology
and structure
Complex cell
wall
Are
Mycobacteria
Gram-
negative or
Gram-
positive?
The phylogenetic position of Mycobacterium
tuberculosis relative to other bacteria is controversial. Its cell
wall has characteristics of both Gram-positive and Gram-
negative bacteria. In the standard reference of bacterial
phylogeny based on 16S ribosomal RNA sequence
comparison, M. tuberculosis belongs to the high G+C Gram-
positive bacteria.
In the genome tree constructed based on conserved gene
content, M. tuberculosis is more related to Gram-negative
than to Gram-positive bacteria as reflected by the
evolutionary distance between nearest ancestral units.
This conclusion may be supported by another analysis
showing that M. tuberculosis shares relatively more
orthologous genes for energy production and conversion
peptidoglycan layer
Peptidoglycan layer linked with arabinose-galactose-mycolic acid
(arabinogalactan mycolate)
Mycolic acids
Major lipids
Long chain (C78-C90)
How long are the acyl
chains of lipids in human
cells?
In lung surfactant?
Free lipids
Waxes: wax D (Freund’s adjuvant)
Helps withstand drying and thus
increases survival
Mycosides: complex saturated
glycolipids
Cord factor: 6,6’-dimycolate of
trehalose
Inhibits neutrophil migration
Thought to mediate granuloma
formation
polypeptides
Act as antigens
Purified protein derivative (PPD)
is used in skin testing
Pathogenesis
Infection via inhalation
of infectious aerosols
No exotoxin or endotoxin
replicates in alveolar
macrophages and can
destroy the cells
“Exported repetitive
protein” prevents the
phagosome from
fusing with the
lysosome
What is the
consequence of this?
nfected macrophages migrate to the local
(tracheobronchial) lymph nodes, the bloodstream and
other tissues
two types of lesion
Exudative: Acute inflammatory response at the initial site of
infection (usually lungs)
Granulomatous: A central area of infected giant cells
(Langhans’cells) surrounded by epithelioid cells (tubercles)
types of lesions
Tubercles may heal spontaneously or may become fibrotic or
calcified
Caseous (cheesy) necrosis and cavitation in the center of the
granuloma, resulting from:
Cellular immune response
Enzymes and reactive oxygen intermediates from dying
macrophages
The exudative lesion and the draining lymph nodes fibrose, and
sometimes calcify, to produce the
Ghon focus seen in X-rays
with associated lymphadenopathy (Ghon complex)
Pulmonary tuberculosis
Latent bacilli can be re-activated when the patient’s immune system
is weakened because of:
malnutrition
alcoholism
diabetes
old age
emotional stress
Pathogenesis and immunity
Intracellular replication stimulates helper and cytotoxic
lymphocytes
T-cells release interferon- and other cytokines
-> Macrophage activation -> MTB killing
Tuberculin skin test: purified protein derivative (PPD)
Positive 4-6 weeks after infection
Localized activated macrophages can penetrate into small
granulomas (< 3 mm) and kill all bacilli
Larger necrotic or caseous granulomas become encapsulated with
fibrin that protects the bacilli
> It is not known how MTB can reside in tissues for years or
decades
four fates
- The initial host response is completely effective and kills all
bacilli; the patient will not develop tuberculosis in the future - The organisms multiply immediately after infection and cause
clinical disease known as primary tuberculosis
Schluger & Rom
Am. J. Respir. Crit. Care Med. 157, 679-691 (1998) - The bacilli may become dormant and never cause disease; the
patient has “latent infection,” evident only by a positive tuberculin
skin test - The latent organisms can eventually grow, with resultant clinical
disease, described as reactivation tuberculosis
epidemiology
Transmitted by aerosols
More common among
The urban poor
Patients with suppressed immune systems
Immigrants from high-incidence areas
> Health care workers are at risk for infection!
clinical syndromes
Primary tuberculosis
mild and asymptomatic
in 90% of cases does not proceed further
In the remaining 10%
Persistent cough, usually for > 3 weeks
Night sweats for weeks or months
Weight loss, malaise, shortness of breath
Elevated temperature
Bloody and purulent sputum
