Mycobacterium

assist. Prof.
Zainab Abdul jabar
Aldhaher
According to the World Health Organization (WHO),
nearly 2 billion people, one-third of the world’s
population, have disease caused by mycobacteria,
particularly tuberculosis.
Mycobacteria are widespread both in the environment
and in animals and cause two major human diseases –
tuberculosis and leprosy. They are aerobic, acid-fast
bacilli (not stained by the Gram stain because of the high
lipid component of the cell wall). The major medically
important pathogens are:
• Mycobacterium tuberculosis, the agent of tuberculosis;
one of the top three infectious diseases affecting humans
globally
Pathogenicity
This organism is the agent of tuberculosis, a
chronic, granulomatous, slowly progressive
infection, usually of the lungs; eventually, many
other organs and tissues may be affected.
A pandemic disease, tuberculosis is especially
common in the developing world owing to HIV
infection (15–20% of individuals with HIV disease
may have tuberculosis).
 Mycobacterium

• Mycobacterium is a genus of Actinobacteria, given

its own family, the Mycobacteriaceae.
• The genus includes pathogens known to cause
serious diseases in mammals, including:
• tuberculosis (Mycobacterium tuberculosis)
• leprosy (Mycobacterium leprae).
• mycobacterium tuberculosis (MTB) is a
pathogenic bacterial species in the genus
Mycobacterium and the causative agent of
most cases of tuberculosis (TB)First
discovered in 1882 by Robert Koch,
• M. tuberculosis has an unusual, waxy coating on
its cell surface (primarily mycolic acid), which
makes the cells impervious to Gram staining, so
acid-fast detection techniques are used, instead.
The physiology of M. tuberculosis is highly aerobic
and requires high levels of oxygen.
 Microbiologic characteristics

• Mycobacteria are aerobic and nonmotile

bacteria.
• Mycobacteria do not contain endospores or
capsules and are usually considered
Gram-positive.
• All Mycobacterium species share a characteristic
cell wall, thicker than in many other bacteria,
which is hydrophobic, waxy, and rich in mycolic
acids/mycolates.
• Many Mycobacterium species adapt readily to
growth on very simple substrates, using ammonia
or amino acids as nitrogen sources and glycerol as
a carbon source in the presence of mineral salts.
Optimum growth temperatures vary widely
according to the species and range from 25 °C to
over 50 °C.
• Some species can be very difficult to culture (i.e.
they are fastidious),
• M. tuberculosis requires oxygen to grow. It does
not retain any bacteriological stain due to high
lipid content in its wall, and thus is neither
Gram-positive nor Gram-negative; hence
Ziehl-Neelsen staining, or acid-fast staining,
• M. tuberculosis divides every 15–20 hours, which
is extremely slow compared to other bacteria,
which tend to have division times measured in
minutes (Escherichia coli can divide roughly every
20 minutes). It is a small bacillus that can
withstand weak disinfectants and can survive in a
dry state for weeks. Its unusual cell wall, rich in
lipids (e.g., mycolic acid), is likely responsible for
this resistance and is a key virulence factor.
symptoms
• Fever
• Malaise – tired, achy
• Lung degeneration – pneumonia
• Chronic cough
• Septicemia, multiple organ failure
• Weight loss despite increased appetite –
“consumption”
Virulence Factors
• Waxy cell wall.
• Major factor is ability to invade and survive
within macrophages as surface protein called
“exported repetitive protein” prevents
phagosome from joining with lysosome.
• It produces no exotoxins or no LPS.
 Pathogenicity

• The organism generally transmitted by droplets

from person with active case of tuberculosis.
• The microorganism is very stable in sputum
droplets and can remain viable in very even dry
sputum for up 6 days.
• M. tuberculosis in droplets is then inhaled and
reach the highly aerobic environment of the lung
where it produce non specific pneumonitis.
• Inflammation occurs such that more
phagocytes travel to the site this is called an
“exudative lesion” end up with a mass of live
and dead bacteria, live and dead phagocytes
surrounded by an outer layer of macrophages
called a granuloma – due to large number of
granulocytes, granuloma becomes surrounded
by fibrin which calcifies called a tubercle, can
be seen by chest X – ray. The infection may
stop at this point and the individual may have
no more symptoms
• The tubercle can break though the lung into
blood vessels and then be disseminated
throughout the body – becomes systemic
infection, 50% mortality rate.
• Tubercle can be coughed up and swallowed,
becoming systemic via the gastrointestinal
tract
• Tubercle can burst years after primery
infection – Reactivation TB
• diagnosis
1. demonstration of acid fast bacilli in smear made
from sputum sample is indicative of tuberculosis.
2. M.tuberculosis can be culture from suptum or other
contaminated fluids onto egg yolk containing agar or
onto oleic acid albumin agar following 2-4 weeks of
incubation.
• The Löwenstein–Jensen medium, is a growth
medium specially used for culture of Mycobacterium
species, notably Mycobacterium tuberculosis.
Löwenstein–Jensen medium
Löwenstein-Jensen agar
When grown on this medium appears as brown, granular
colonies (sometimes called "buff, rough and tough"). The
medium must be incubated for a significant length of
time, usually four weeks, due to the slow doubling time
of M. tuberculosis (15–20 hours) compared with other
bacteria.
3. Chest X – ray
4. Tuberculin skin test (Mantoux Test)
Purified protein derivative (PPD), part of cell wall is
injected under the skin, 24 – 48 hours measure the size of
the welt that forms. Cell have been primed and recognize
the PPD.
o Positive reaction means you have been
exposed to the organism:
• Could have active infection
• Could have been infected but were one of the
90% who are Asymptomatic.
• You have been immunized
 Antigenic structure:

• The mycobacterial antigens have been classified

as:
• 1- Soluble (cytoplasmic) and insoluble (cell wall
lipid bound).
• 2- Carbohydrates or proteins
• 3- by their distribution within the genus
 Treatment
• Antibiotic sensitivity and control
Long-term therapy (6–9 months) with antituberculous
drugs (isoniazid, rifampicin, pyrazinamide, ethambutol).
As drug resistance is growing and a persistent problem,
combination therapy should always be given. Tubercle
bacilli resistant to a number of antituberculous drugs
(multidrug-resistant tuberculosis (MDR-TB)) is a
growing problem. Hence, regimentation of drug delivery is
a cornerstone of managing the disease, which is achieved
by a global programme termed directly observed therapy
(DOT). Prevention is by bacille Calmette–Guérin (BCG)
vaccination containing live attenuated organisms, in
childhood.
vaccine
BCG (Bacilli Calmete Guerin) vacine
• Made to stimulate the cell mediated immune
response as M. tuberculosis is largely an
intracellular pathogen
• Uses live attenuated M. bovis, causes TB in cows
• Most effective in children, given as part of early
childhood regime in endemic regions
• Some cases of human contracting M. bovis from
vaccine, or from drinking unpasteurized milk
from infected cow.