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Mycobacterium tuberculosis and Tuberculosis (page 1)
(This chapter has 4 pages)
© Kenneth Todar, PhD
Tuberculosis (TB) is the leading cause of death in the world
from a bacterial infectious disease. The disease affects 1.8 billion
which is equal to one-third of the entire world population.
In the United States TB is on the decline. In 2007 a total of
13,293 cases were reported. The TB rate declined to 4.4
cases per 100,000 population, the lowest recorded rate since national
reporting began in 1953. Despite this overall improvement, progress
toward TB elimination has
slowed in recent years; the average annual percentage decline in the TB
rate slowed from 7.3% per year during 1993--2000 to 3.8% during
2000--2007. Also, since 1993 there has been a gradual decline in the
of TB patients with coinfection with HIV, and the number of cases of
multiple drug-resistant TB has gradually dropped.
On the other hand, the proportion of TB cases contributed by
foreign-born persons has increased each year since 1993. In 2007 the
TB rate in foreign-born persons in the United States was 9.7 times
higher than in U.S.-born persons. In many states, especially in the
upper Midwest, and the Northeast, most new cases of TB now occur in
individuals who are foreign born.
This and more information on the epidemiology of TB in the United
States, provided by the CDC Division
of Tuberculosis Elimination, is provided at the end of this
chapter. First things first: Mycobacterium
tuberculosis and the disease tuberculosis.
Mycobacterium tuberculosis scanning
electron micrograph. Mag 15549X. CDC.
Mycobacterium tuberculosis is the etiologic agent of
in humans. Humans are the only reservoir for the bacterium.
Mycobacterium bovis is the etiologic agent of TB in
and rarely in humans. Both cows and humans can serve as reservoirs.
can also be infected by the consumption of unpasteurized milk. This
of transmission can lead to the development of extrapulmonary TB,
exemplified in history by bone infections that led to hunched backs.
Other human pathogens belonging to the Mycobacterium genus
avium which causes a TB-like disease especially prevalent in
patients, and Mycobacterium leprae, the causative agent
History and Present Day Importance
Mycobacterium tuberculosis (MTB) was the cause of the
Plague" of the 17th and 18th centuries in Europe. During this period
100 percent of the European population was infected with MTB,
25 percent of all adult deaths were caused by MTB (Note: The White
is not to be confused with the "Black Plague", which was caused by Yersinia
pestis and occurred about 3 centuries earlier).
Mycobacterium tuberculosis is a fairly large nonmotile
bacterium distantly related to the Actinomycetes. Many non
mycobacteria are components of the normal flora of humans, found most
in dry and oily locales. The rods are 2-4 micrometers in length and
Mycobacterium tuberculosis is an obligate aerobe. For
this reason, in the classic case of tuberculosis, MTB complexes
always found in the well-aerated upper lobes of the lungs. The
is a facultative intracellular parasite, usually of
and has a slow generation time, 15-20 hours, a physiological
that may contribute to its virulence.
Two media are used to grow MTB Middlebrook's medium which
an agar based medium and Lowenstein-Jensen medium which is an
based medium. MTB colonies are small and buff colored when grown on
medium. Both types of media contain inhibitors to keep contaminants
out-growing MT. It takes 4-6 weeks to get visual colonies on either
Colonies of Mycobacterium tuberculosis
on Lowenstein-Jensen medium. CDC.
Chains of cells in smears made from in vitro-grown colonies often
distinctive serpentine cords. This observation was first made
Robert Koch who associated cord factor with virulent strains of
MTB is not classified as either Gram-positive or
because it does not have the chemical characteristics of either,
the bacteria do contain peptidoglycan (murein) in their cell wall. If a
Gram stain is performed on MTB, it stains very weakly Gram-positive
not at all (cells referred to as "ghosts").
Mycobacterium species, along with members of a related genus
are classified as acid-fast bacteria due to their
by certain dyes and stains. Despite this, once stained, acid-fast
will retain dyes when heated and treated with acidified organic
One acid-fast staining method for Mycobacterium tuberculosis is
the Ziehl-Neelsen stain. When this method is used, the MTB.
is fixed, stained with carbol-fuchsin (a pink dye), and decolorized
acid-alcohol. The smear is counterstained with methylene-blue or
other dyes. Acid-fast bacilli appear pink in a contrasting background.
In order to detect Mycobacterium tuberculosis in a sputum
sample, an excess of 10,000 organisms per ml of sputum are needed to
the bacilli with a 100X microscope objective (1000X mag). One acid-fast
is regarded as "suspicious" of an MTB infection.
Mycobacterium tuberculosis. Acid-fast
Cell Wall Structure
The cell wall structure of Mycobacterium tuberculosis
special attention because it is unique among procaryotes, and it is a
determinant of virulence for the bacterium. The cell wall complex
but otherwise it is composed of complex lipids. Over 60% of the
cell wall is lipid. The lipid fraction of MTB's cell wall consists of
three major components, mycolic acids, cord factor, and wax-D.
Mycolic acids are unique alpha-branched lipids found in cell
walls of Mycobacterium and Corynebacterium. They make
50% of the dry weight of the mycobacterial cell envelope. Mycolic
acids are strong hydrophobic molecules that form a lipid shell around
organism and affect permeability properties at the cell surface.
Mycolic Acids are thought to be a significant determinant of
in MTB. Probably, they prevent attack of the mycobacteria by cationic
proteins, lysozyme, and oxygen radicals in the phagocytic granule.
They also protect extracellular mycobacteria from complement deposition
Cord Factor is responsible for the serpentine cording
above. Cord factor is toxic to mammalian cells and is also an inhibitor
of PMN migration. Cord factor is most abundantly produced in virulent
Wax-D in the cell envelope is the major component of Freund's
complete adjuvant (CFA).
The high concentration of lipids in the cell wall of Mycobacterium
tuberculosis have been associated with these properties of the
Impermeability to stains and dyes
Resistance to many antibiotics
Resistance to killing by acidic and alkaline compounds
Resistance to osmotic lysis via complement deposition
Resistance to lethal oxidations and survival inside of macrophages