Mycobacterium tuberculosisPathogenesis and Molecular Determinants of Virulence

Abstract

Tuberculosis (TB), one of the oldest known human diseases. is still is one of the major causes of mortality, since two million people die each year from this malady. TB has many manifestations, affecting bone, the central nervous system, and many other organ systems, but it is primarily a pulmonary disease that is initiated by the deposition of Mycobacterium tuberculosis, contained in aerosol droplets, onto lung alveolar surfaces. From this point, the progression of the disease can have several outcomes, determined largely by the response of the host immune system. The efficacy of this response is affected by intrinsic factors such as the genetics of the immune system as well as extrinsic factors, e.g., insults to the immune system and the nutritional and physiological state of the host. In addition, the pathogen may play a role in disease progression since some M. tuberculosis strains are reportedly more virulent than others, as defined by increased transmissibility as well as being associated with higher morbidity and mortality in infected individuals. Despite the widespread use of an attenuated live vaccine and several antibiotics, there is more TB than ever before, requiring new vaccines and drugs and more specific and rapid diagnostics. Researchers are utilizing information obtained from the complete sequence of the M. tuberculosis genome and from new genetic and physiological methods to identify targets in M. tuberculosis that will aid in the development of these sorely needed antitubercular agents

Interaction of Nanoparticles in Biological Systems and their Role in Therapeutical Treatment of Tuberculosis and Cancer

“…TB infection is generally initiated by the access of bacilli to the respiratory system in aerosol droplets Singh et al, 2011;Rajni et al, 2011). These bacteria engulfed by alveolar macrophages that process the bacterial antigens and present them to lymphocytes T (Smith et al, 2003). Then these bacilli augment exponentially by invading host cells and spread locally to regional lymph nodes in the lungs by lymphatic circulation (3-8 weeks post infection).…”

“…Second line drugs are less effective, more toxic, and more expensive than the first line drugs. And to assure therapeutic effectiveness, these drugs are administered for longer duration (9-12 months) resulting in patient's non-compliance (Smith et al, 2003). Novel drugs employing NPs are particularly designed to overcome drug resistance; for shortening the treatment duration and to reduce drug interactions with the other anti-retroviral therapies.…”

Zoonotic aspects of Mycobacterium bovis and Mycobacterium avium-intracellulare complex (MAC)

“…These organisms share some of the same physiological characteristics and molecular determinants of virulence described for other slowly growing mycobacteria as M. tuberculosis or M. leprae, see [49,82,158] for a review. These organisms are surrounded by a cell wall and an envelope characteristic of mycobacteria which confers their distinctive feature of acid fastness [82].…”

“…The bacteria of the genus Mycobacterium are Gram-positive, acid-fast organisms that include a number of major human and animal pathogens [49,142,158]. Although human tuberculosis is caused mainly by M. tuberculosis, M. bovis the etiological agent of bovine tuberculosis can also be responsible for human disease, which makes this bacterium an important zoonotic species (see Fig.…”

The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

“…Although the complete genome sequencing of M. tuberculosis has been a landmark in mycobacterial research (Cole et al 1998), the genetic determinants of M. tuberculosis virulence are not completely understood yet (Smith 2003). This is partly due to the difficulty in constructing mutants of M. tuberculosis, especially by gene replacement (Morsczeck 2003).…”