Essay About Persistence Of M. Tuberculosis And Conventional Anti-Tuberculosis Drugs

Stress Response in Tb
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Summary
Mycobacterium tuberculosis is a successful pathogen that over-
comes numerous challenges presented by the immune system of the
host. This bacterium usually establishes a chronic infection in the host
where it may silently persist inside a granuloma until, a failure in host
defenses, leads to manifestation of the disease. None of the
conventional anti-tuberculosis drugs are able to target these persisting
bacilli. Development of drugs against such persisting bacilli is a
constant challenge since the physiology of these dormant bacteria is
still not understood at the molecular level. Some evidence suggests
that the in vivo environment encountered by the persisting bacteria is
anoxic and nutritionally starved. Based on these assumptions,
anaerobic and starved cultures are used as models to study the
molecular basis of dormancy. This review outlines the problem of
persistence of M. tuberculosis and the various in vitro models used to
study mycobacterial latency. The basis of selecting the nutritional
starvation model has been outlined here. Also, the choice of M.
smegmatis as a model suitable for studying mycobacterial latency is
discussed. Lastly, general issues related to oxidative stress and
bacterial responses to it have been elaborated. We have also discussed
general control of OxyR-mediated regulation and emphasized the
processes which manifest in the absence of functional OxyR in the
bacteria. Lastly, a new class of protein called Dps has been reviewed
for its important role in protecting DNA under stress.
IUBMB Life, 57: 149 – 159, 2005
Keywords Mycobacteria; latency; nutritional starvation; Dps;
OxyR; Regulon.
If the importance of a disease for mankind is measured by the
number of fatalities it causes, then tuberculosis must be
considered much more important than those most feared
infectious diseases, plague, cholera and the like. One in seven
of all human beings die from tuberculosis. If one only
considers the productive middle-age groups, tuberculosis
carries away one-third, and often more.
Robert Koch, 24 March, 1882
INTRODUCTION
Mycobacterium tuberculosis: A Successful Pathogen
Despite the efforts for more than a century since Koch
discovered Mycobacterium tuberculosis, there are still many
infected individuals and around two million deaths occur
annually from tuberculosis.
The main route of infection for the tubercle bacillus is the
respiratory tract, where the bacteria, inhaled in airborne
droplets, are released in the environment by an already infected
patient through coughing. The bacteria then travel to lungs and
establish an infection (1). In the lungs they п¬Ѓrst encounter
alveolar macrophage, which has the ability to destroy most
potential invaders. However, M. tuberculosis has the extra-
ordinary ability to persist and even replicate in this extremely
hostile environment, where most other pathogens would perish.
M. tuberculosis seems to have evolved effective strategies to
survive most of the macrophage killing mechanisms.