MYCOBACTERIUM

Acid Fast Bacilli

Asst. Prof.
Dr. Nadia Hameed Mohammed
MBChB-FIBMS Board Pathology (Micro/Immun)
 Mycobacterium
Domain: Bacteria

Phylum: Actinomycetota

Class: Actinomycetia

Order: Mycobacteriales

Family: Mycobacteriaceae

Genus: Mycobacterium
 MYCOBACTERIUM

• Mycobacteria are aerobic bacilli.

• Neither gram-positive nor gram-negative
• This bacteria is acid-fast bacteria by its ability
to retain the carbolfuchsin stain despite
subsequent treatment with an
ethanol–hydrochloric acid mixture due to
high lipid content (approximately 60%) of their
cell wall.
Mycobacterium
 Mycobacterium spp
Classification of mycobacterium
I// Mycobacterium tuberculosis complex:
a. Mycobacterium tuberculosis, the cause of pulmonary
tuberculosis
b. Mycobacterium leprae, the cause of leprosy.
c. Mycobcterium bovis, the cause of intestinal tuberculosis

These are the clinically important MO

 Mycobacterium

II// Atypical Mycobacterium:

Include mycobacterium spp other than Mycobacterium
tuberculosis (MOTT).
These bacterium classified to four groups according to
their
1. Rate of growth
2. Whether they produce pigment under certain
conditions
Group I (photochromogens): grow slowly (> 1week)
• produce a yellow-orange–pigmented colony only when exposed to light
• Mycobacterium kansasii causes lung disease clinically resembling
tuberculosis.
Group II (scotochromogens): grow slowly (> 1week)
• produce the pigment chiefly in the dark
• Mycobacterium scrofulaceum causes scrofula, a granulomatous cervical
adenitis, usually in children but still Mycobacterium tuberculosis is the
main cause of disease.

Group III (nonchromogens): grow slowly (> 1week)

• produce little or no yellow-orange pigment
• Mycobacterium avium–intracellulare complex.
• They cause pulmonary disease clinically indistinguishable from
tuberculosis, primarily in immunocompromised patients

Group IV: are “rapid growers,” producing colonies in fewer than 7 days.
M. fortuitum and M. chelonae. They are saprophytes, found chiefly in soil and
water, cause human disease in immunocompromised patients or those in
whom prosthetic devices have been implanted .
 Mycobacterium Tuberculosis (MTB)

• These bacteria are Bacilli , straight or slightly curved

occurring singly or in pairs or in small groups
• None Spore former, none motile and
• obligate Aerobic that derive energy from the oxidation
of many simple carbon compounds.
• Increased CO2 tension enhances growth.
• True tubercle bacilli are characterized by “acid fastness
• MTB has hydrophobic surface that make it resist
chemical agents including acids, alkalines, dyes and
antibiotics
• MTB resist dryness (dehydration) and survive for long
periods in dried sputum.
 MTB
Constituents of Tubercle Bacilli
The three main layers of the cell wall are
• Peptidoglycan (PG),
• Lipopolysaccharides: arabinogalactan AG
(lipoarabinomannan LAM, and lipomannan LM)
• Outer membrane, which contains mycolic acids MA
 MTB
Chemical components of the cell wall are:
A. Lipid: Mycobacterial cell wall rich in lipids.
These include mycolic acids (long-chain fatty
acids C78–C90), waxes, and phosphatides. In the
cell, the lipids are largely bound to proteins and
polysaccharides and lead to granuloma
formation; and caseous necrosis..
 MTB
Mycolic acid has responsible for:
a.Acid fastness
b.Give hydrophopic character to the tubercle
c.It bound to other saccharides to form trehalose
dimycolates (cord factor).Virulent strains of tubercle
bacilli form microscopic “serpentine cords” in which
acid-fast bacilli are arranged in parallel chains due to
presence of“cord factor”
 MTB
Cord factor is correlated with virulence of the bacteria because:
1.It inhibits migration of leukocytes
2.Causes chronic granulomas
3.Serve as an immunologic adjuvant.
 MTB

B. Proteins Each type of mycobacterium contains

several proteins that bound to wax and elicit the
tuberculin reaction. They can also elicit the
formation of a variety of antibodies.

C. Polysaccharides: Mycobacteria contain a variety

of polysaccharides. Their role in the pathogenesis of
disease is uncertain. They can induce the immediate
type of hypersensitivity and can serve as antigens in
reactions with sera of infected persons.
 MTB
Disease:
• Pulmonary tuberculosis,
• Extraplmonary tuberculosis
• Military TB
 MTB
Transmission and epidemiology:
MTB is transmitted from person to person by respiratory aerosols
produced by coughing.
Risk of exposure to infection increase in
1.Area with high rate of active infection
2.Crowding and poor aeration
3.Low socioeconomic state
4.Inadequacy of medical care

Risk of developing clinical disease depends on:

1.Genetic susceptibility ie those withHLA-Bw15 more susceptible
2.Inoculum dose
3.Host status including Age (high risk in infancy and in elderly adults),
Undernutrition, Immunologic status, Coexisting diseases (eg,
diabetes)…..
 MTB
• Approximately one-third of the world’s population is
infected with this organism.
• Each year, it is estimated that 1.7 million people die of
tuberculosis
• 9 million new cases each year.
• An estimated 500,000 people are infected with a multidrug-
resistant strain of MTB
• About 20% of people are infected by aerosols produced by
the coughing of “smear-negative” people.
• Mycobacterium bovis also causes tuberculosis in humans. It
is found in cow’s milk, which, unless pasteurized, can cause
gastrointestinal tuberculosis in humans.
 MTB
Pathogenesis:

Mycobacteria are emitted in droplets smaller than 25 μm

in diameter when infected persons cough, sneeze, or
speak. The organism deposited in alveoli. Inside the
alveoli, the host’s immune system responds by release of
cytokines and lymphokines that stimulate monocytes
and macrophages. Mycobacteria begin to multiply within
macrophages. Some of the macrophages develop an
enhanced ability to kill the organism, but others may be
killed by the bacilli. One to 2 months after exposure,
pathology of the lesions associated with infection appear
in the lung.
 MTB
Pathogenesis.. cont.
• Mycobacterium tuberculosis produces no exotoxins
• The organism preferentially infects macrophages and
other reticuloendothelial cells.
• survives and multiplies withina cellular vacuole called
a phagosome.
• The organism produces a protein called “exported
repetitive protein” that prevents the phagosome from
fusing with the lysosome, thereby allowing the
organism to escape the degradativeenzymes in the
lysosome
 MTB
Pathogenesis…. cont
Tubercle bacilli spread in the host by
• direct extension
• through the lymphatic channels
• Bloodstream
• through bronchi and pharynx swallowed to
gastrointestinal tract
 MTB
Pathology
1. Exudative type—This consists of an acute
inflammatory reaction with edema fluid;
polymorphonuclear leukocytes; and, later,
monocytes around the tubercle bacilli. This type is
seen particularly in lung tissue at the initial site of
infection. During the exudative phase, the tuberculin
test result becomes positive. This lesion usually
healed by resolution or may develop into the second
(productive) type of lesion.
 MTB
Pthology …cont.
2. Productive type (granulomatous lesion)—
characterized by granuloma formation. granulom
consists of three zones: (1) a central area of caseous
necrosis (2) a mid zone of pale epithelioid cells, often
arranged radially; and large, multinucleated giant cells
containing tubercle bacilli; (3) a peripheral zone of
fibroblasts, lymphocytes, and monocytes.
• Such a lesion is called a tubercle. A caseous tubercle
may break into a bronchus, empty its contents there,
and form a cavity. It may subsequently heal by fibrosis
or calcification.
 MTB
Types of tuberculosis infection

I// Primary tuberculosis (primary TB )

II// Secondary infection (reactivation TB,

secondary TB)
 MTB
I//Primary Tuberculosis
•Primary tuberculosis occurs in a person lacking previous
contact with the tubercle bacillus.
•Acquired by inhaling droplet that contains the tubercle
bacillus.
•Affect the lower lobes.
•Soon after entering the lung, the bacilli are surrounded and
engulfed by macrophages and gray-white, circumscribed
granuloma formed. This granulomatous lesion in the lower
lobes of the lung, called a Ghon’s focus
•Tubercle bacilli, free or inside macrophages, drain along the
lymph channels to the hillar lymph nodes of the affected lung
and there evoke the formation of lymph nodes caseous
necrosis and granulomas formation.
•The combination of the primary lung lesion and lymph node
granulomas is called Ghon’s complex .
 MTB
Outcome of primary TB:
1. Primary tuberculosis usually is asymptomatic, with the
only evidence of the disease being a positive tuberculin skin
test result and calcified lesions seen on the chest radiograph.
2. In immune compromised patients, primary tuberculosis
may progress, causing more extensive destruction of lung
tissue (progressive lung disease)
3. Sever bacteremia and the infection spread to the lung
and to the other body organs (military TB).
4. After lung infection, blood and lymphatic
dissemination, dormant tubercle bacilli may progress to
secondary TB in the lung and extrapulmonary TB.
 MTB
II//Secondary Tuberculosis

•Secondary tuberculosis represents either reinfection from

inhaled droplet as in endemic areas or reactivation of a
previously healed primary lesion (only 5% of primary TB
develops secondary TB in developed countries).
•It often occurs in situations of impaired body defense
mechanisms.
•It is classically localized to the apex of one or both upper
lobes.
•The regional Lymph nodes involvement is less prominently
than they are in primary TB
•Cavitation occurs which leads to erosion of airways and this
converts the patient into source of infection to others.
Miliary TB
 MTB
Clinical featres:
• The primary disease asymptomaic in 90% of cases.
• Fatigue, weakness, weight loss, fever, and night sweats
cough and hemoptysis may be signs of tuberculous disease.
• Because the tubercle bacillus can involve every organ
system, its clinical manifestations are protean and patient may
present with signs and symptoms of infection of the affected
organ urinary infection –dysuria , intestinal infection –
abdominal pain…
• Scrofula is mycobacterial cervical lymphadenitis that
presents as swollen, nontender lymph nodes, usually
unilaterally
• Erythema nodosum, characterized by tender
nodules along the extensor surfaces of the tibia and
ulna, is a manifestation of primary infection seen in
patients who are controlling the infection with a
potent cell-mediated response.
• TB should be involved in the differential
diagnosis of the following states:
1. PUO pyrexia of unknown origion
2. Infections not respond to treatment
3. Chronic cough (cough >1 month )