Genomic Variability of Mycobacterium tuberculosis

Science, 2010

Mycobacterium tuberculosis has a penetrance of its host population that would be the envy of most human pathogens. About one-third of the human population would have a positive skin test for the infection and is thus thought to harbor the bacterium. Globally, 22 "high-burden" countries account for more than 80% of the active tuberculosis cases in the world, which shows the inequitable distribution of the disease. There is no effective vaccine against infection, and current drug therapies are fraught with problems, predominantly because of the protracted nature of the treatment and the increasing occurrence of drug resistance. Here we focus on the biology of the host-pathogen interaction and discuss new and evolving strategies for intervention.

Indian Journal of Medical Research, 2017

Indian Journal of Pharmaceutical Sciences, 2016

Several potent drugs have been available for the treatment of tuberculosis (TB) since past 70 years. However, poor management of tuberculosis continues to take a heavy count of human lives [1,2]. The disease has become prevalent in countries like Africa, India, China and Russia [3-5]. In India nearly 500,000 people die every year due to this dreadful disease [6-10]. In the early times, in the absence of any cure, infected patients faced slow and painful death. Many patients died unattended in infirmaries [11-13]. There are about 10 million new tuberculosis cases added every year worldwide [14]. About 2 million people succumb to this life threatening disease [15]. Some of the main factors which has contributed to this death dealing disease are the absence of basic sanitary facilities and the emigration of people from rural to urban crowded slums [16-18]. Tuberculosis is caused by rod shaped, aerobic, acid fast, gram positive bacteria named Mycobacterium tuberculosis which was first identified by a German Physician, Robert Koch, in 1882 (Table 1) [6,7]. The bacterium exists in both latent and active forms.

Journal of medical microbiology, 2015

Some species of the Mycobacterium tuberculosis complex (MTBC), particularly Mycobacterium tuberculosis that causes human tuberculosis (TB), are the first cause of death linked to a single pathogen worldwide. In the last decades, evolutionary studies have much improved our knowledge on MTBC history and have highlighted its long co-evolution with humans. Its ability to remain latent in humans, the extraordinary proportion of asymptomatic carriers (1/3 of the entire human population), the deadly epidemics and the observed increasing level of resistance to antibiotics are proofs of its evolutionary success. Many MTBC molecular signatures show that these bacteria are not only a model of adaptation to humans, but that they have also influenced human evolution. Due to the unbalance between the number of asymptomatic carriers and the number of patients with active TB, some authors suggest that infection by MTBC could have a protective role against active TB disease and also against other pa...

International Journal of Pediatrics, 2016

Background Tuberculosis (TB) is the second-most common cause of death from infectious disease (after those due to HIV/AIDS). Roughly one-third of the world's population has been infected with M. tuberculosis, with new infections occurring in about 1% of the population each year. People with active TB can infect 10-15 other people through close contact over the course of a year.

2013

Tuberculosis (TB) remains one of the world's most deadly infectious diseases, with approximately 1.5 million deaths and 9 million new cases of TB in 2010. There is an urgent global need to develop new control tools, with advances necessary in our basic understanding of the pathogen, Mycobacterium tuberculosis, and translation of these findings to public health. It was in this context that the "Tuberculosis 2012: Biology, Pathogenesis, Intervention Strategies" meeting was held in the Institut Pasteur, Paris, France from 11 to 15th Sept 2012. The meeting brought together over 600 delegates from across the globe to hear updates on the latest research findings and how they are underpinning the development of novel vaccines, diagnostics, and drugs.

Virulence, 2013

European Journal of Pediatrics, 2008

Directly observed standardized short-course chemotherapy (DOTS) regimes are an effective treatment for drug susceptible tuberculosis disease. Surprisingly, DOTS has been reported to reduce the transmission of multi-drug resistant tuberculosis, and standardized short-course chemotherapy regimens with first-line agents have been found to be adequate treatments for some patients with drug resistant tuberculosis, including multi-drug resistance. These paradoxical observations and the apparent heterogeneity in treatment outcome of multi-drug resistant tuberculosis when using standard regimens may be due in part to limitations of in vitro drug susceptibility testing based on unique but mistakenly used techniques in diagnostic mycobacteriology. Experimental data and mathematical models indicate that the fitness cost conferred by a resistance determinant is the single most important parameter which determines the spread of drug resistance. Chromosomal alterations that result in resistance to firstline antituberculosis agents, e.g. isoniazid, rifampicin, streptomycin, may or may not be associated with a fitness cost. Based on work in experimental models and from observations in clinical drug resistant isolates a picture emerges in which, among the various resistance mutations that appear with similar rates, those associated with the least fitness cost are selected in the population.

The Lancet. Respiratory medicine, 2017

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbi...