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Nobody does it better: Mycobacterium tuberculosis and persistence

In the evolution of lifeforms, the purpose is to survive.
---- Ray Kurzweil, The Singularity Is Near

Like Ian Fleming’s Agent 007, the bacterium Mycobacterium tuberculosis (Mtb) has a reputation of survival and intrigue that surpasses all the other guys in the field. Mtb, the causative agent of tuberculosis (TB), has persisted in the public domain for centuries and has been called the world’s most successful pathogen. The tubercle bacilli have found survival success in multiple pathways to sidetrack infected host cells from an effective immune response to a less than proficient response, allowing bacterial persistence. Mtb infects about one-third of the world’s human population, and each year results in more than 2 million deaths.

Tuberculosis or the “Great white plague”, also known as consumption, is among the deadliest of all human infectious diseases. Moreover, Mtb resides as a persistent infection, the hallmark of tuberculosis, in an estimated 2 billion people who lack clinical symptoms and are not infectious (latent TB). About 10 percent of those latently infected, upon activation to TB disease, have the potential to drive the transmission of TB and serve as the largest reservoir of tubercle bacilli.

Transmitted through aerosols, droplets containing one to three bacilli may be inhaled when a person with TB disease (active TB) of the lungs or throat coughs, sneezes, or speaks, leading to infection of nearby individuals. Mtb usually settles in the lungs, but may affect other body parts, for instance, the kidneys, spine, and brain. Untreated or treated improperly, TB disease can be fatal.

A worldwide resurgence of tuberculosis has been noted, especially in developing countries. Several factors have contributed to the resurgence of this chronic infectious disease, including increased populations in close living quarters, greater numbers of susceptible individuals, and multiple drug-resistant Mtb strains. In countries with reportedly high transmission rates of TB and human immunodeficiency virus (HIV) co-infection, new TB cases often present with drug resistance.

In the genus Mycobacterium, which encompasses over 120 species, the different species are commonly divided into fast-growers and slow-growers. The fast-growers such as Mycobacterium smegmatis are generally harmless, while slow-growers include some of the most important human pathogens, namely Mtb, and Mycobacterium leprae, which causes leprosy (Hansen’s disease) and is closely related to Mtb. Leprosy, though not fatal, is a leading source of nontraumatic peripheral nerve damage the world over.

Mtb is the best known and most important member of the Mycobacterium tuberculosis complex. The Mtb complex comprises four other species that cause TB: M. africanum (human), M. canetti (human), M. microti (rodents), and M. bovis (cattle). Typically, the Mtb complex members share at least 99% nucleotide sequence similarity and comparable pathologies, prompting the proposal that the bacterial forms, adapted to different hosts, should be reclassified ‘ecotypes of M. tuberculosis’ rather than species.

Within the genus Mycobacterium are other species and subspecies significant to human and animal welfare, which do not cause TB (nontuberculous mycobacteria [NTM]) or leprosy, yet some are virulent among them: M. kansasii, M. ulcerans, and M. marinum. The NTM can cause pulmonary disease similar in presentation to TB including skin disease and disseminated disease. The M. avium complex (MAC) represents a group of widespread opportunistic pathogens among the NTM, which can cause swelling of the lymph nodes or glands in the face and neck, especially in children.

The Stop TB Partnership, an international body with a wide range of constituencies and hosted by the World Health Organization (WHO) in Geneva, Switzerland, has set the visionary goals to: 1) halve TB prevalence and mortality by 2015 and 2) eliminate TB by 2050. The plan is recognized and supported by global partners and organizations.

The next articles will offer more insights into M. tuberculosis: the views of two researchers with long-established expertise in TB and information on some of the mechanisms that foster Mtb's survival.

References and Read-more-about-it
1. Sizemore CF, Schleif AC, Bernstein JB, Heilman CA. The role of biomedical research in global tuberculosis control: gaps and challenges. A perspective from the US National Institute of Allergy and Infectious Diseases, National Institutes of Health. Emerging Microbes and Infections 2012; 1: 1-6.
2. Hingley-Wilson SM, Sambandamurthy VK, Jacobs Jr. WR. Survival perspective from the world’s most successful pathogen, Mycobacterium tuberculosis. Nat Immunol. 2003; 4: 949-955.
3. Sacchettini JC, Rubin EJ, Freundlich JS. Drugs versus bugs: in pursuit of the persistent predator Mycobacterium tuberculosis. Nat Rev Microbiol. 2008 Jan;6(1):41-52.
4. Smith NH, Hewinson RG, Kremer K et al. Myths and misconceptions: the origin and evolution of Mycobacterium tuberculosis. Nat Rev Microbiol. 2009;7:537-44.
5. Centers for Disease Control and Prevention. Tuberculosis (TB). Available at: (Accessed 04 January 2013).
6. Harries AD, Dye C. Centennial Review Tuberculosis. Annals of Tropical Medicine and Parasitology 2006;100 (5&6):415-431.
7. Penheiro RO, de Souza Salles J, Sarno EN, Sampaio EP. Mycobacterium leprae–host-cell interactions and genetic determinants in leprosy: an overview. Future Microbiol. 2011 Feb; 6(2):217-230.
8. van Ingen J, Boeree MJ, van Soolingen D et al. Are phylogenetic position, virulence, drug susceptibility and in vivo response to treatment in mycobacteria interrelated? Infection, Genetics, and Evolution 2012; 12:832-837.


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