Mycobacterium tuberculosis

Behavior

M. tuberculosis was found in 2019 a complex that has at least 9 members: ''M. tuberculosis'' ''sensu stricto'', ''M. africanum, M. canetti, M. bovis, M. caprae, M. microti'', ''M. pinnipedii'', ''M. mungi,'' and ''M. orygis''. It requires oxygen to grow, it is debated whether it produces spores, and is nonmotile. ''M. tuberculosis'' divides every 18–24 hours. This is extremely slow compared with other bacteria, which tend to have division times measured in minutes . It is a small bacillus that can withstand weak disinfectants and can survive in a dry state for weeks. Its unusual cell wall is rich in lipids such as mycolic acid, is likely responsible for its resistance to desiccation and is a key virulence factor.

Evolution

The ''M. tuberculosis'' complex evolved in Africa and most probably in the Horn of Africa. In addition to ''M. tuberculosis'', the ''M. tuberculosis'' complex has a number of members infecting various animal species, these include ''M. africanum'', ''M. bovis'' , ''M. caprae'', ''M. microti'', ''M. mungi, M. orygis'', and ''M. pinnipedii''. This group may also include the ''M. canettii'' clade. These animal strains of MTBC do not strictly deserve species status, as they are all closely related and embedded in the ''M. tuberculosis'' phylogeny, but for historic reasons, they currently hold species status.

The ''M. canettii'' clade – which includes ''M. prototuberculosis'' – is a group of smooth-colony ''Mycobacterium'' species. Unlike the established members of the ''M. tuberculosis'' group, they undergo recombination with other species. The majority of the known strains of this group have been isolated from the Horn of Africa. The ancestor of ''M. tuberculosis'' appears to be ''M. canettii'', first described in 1969.

The established members of the ''M. tuberculosis'' complex are all clonal in their spread. The main human-infecting species have been classified into seven lineages. Translating these lineages into the terminology used for spoligotyping, a very crude genotyping methodology, lineage 1 contains the East African-Indian , the Manila family of strains and some Manu strains; lineage 2 is the Beijing group; lineage 3 includes the Central Asian strains; lineage 4 includes the Ghana and Haarlem , Latin America-Mediterranean and X strains; types 5 and 6 correspond to ''M. africanum'' and are observed predominantly and at high frequencies in West Africa. A seventh type has been isolated from the Horn of Africa. The other species of this complex belong to a number of spoligotypes and do not normally infect humans.

Lineages 2, 3 and 4 all share a unique deletion event and thus form a monophyletic group. Types 5 and 6 are closely related to the animal strains of MTBC, which do not normally infect humans. Lineage 3 has been divided into two clades: CAS-Kili and CAS-Delhi .

Lineage 4 is also known as the Euro-American lineage. Subtypes within this type include Latin American Mediterranean, Uganda I, Uganda II, Haarlem, X, and Congo.

A much cited study reported that ''M. tuberculosis'' has co-evolved with human populations, and that the most recent common ancestor of the ''M. tuberculosis'' complex evolved between 40,000 and 70,000 years ago. However, a later study that included genome sequences from ''M. tuberculosis'' complex members extracted from three 1,000-year-old Peruvian mummies, came to quite different conclusions. If the most recent common ancestor of the ''M. tuberculosis'' complex were 40,000 to 70,000 years old, this would necessitate an evolutionary rate much lower than any estimates produced by genomic analyses of heterochronous samples.

An analysis of over 3000 strains of ''M. bovis'' from 35 countries suggested an Africa origin for this species.There are currently two narratives existing in parallel regarding the age of MTBC and how it has spread and co-evolved with humans through time. One study compared the ''M. tuberculosis'' phylogeny to a human mitochondrial genome phylogeny and interpreted these as being highly similar. Based on this, the study suggested that ''M. tuberculosis'', like humans, evolved in Africa and subsequently spread with anatomically modern humans out of Africa across the world. By calibrating the mutation rate of M. tuberculosis to match this narrative, the study suggested that MTBC evolved 40,000–70,000 years ago. Applying this time scale, the study found that the ''M. tuberculosis'' effective population size expanded during the Neolithic Demographic Transition and suggested that ''M. tuberculosis'' was able to adapt to changing human populations and that the historical success of this pathogen was driven at least in part by dramatic increases in human host population density. It has also been demonstrated that after emigrating from one continent to another, a human host's region of origin is predictive of which TB lineage they carry, which could reflect either a stable association between host populations and specific ''M. tuberculosis'' lineages and/or social interactions that are shaped by shared cultural and geographic histories.

Regarding the congruence between human and ''M. tuberculosis'' phylogenies, a study relying on ''M. tuberculosis'' and human Y chromosome DNA sequences to formally assess the correlation between them, concluded that they are not congruent. Also, a more recent study which included genome sequences from ''M. tuberculosis'' complex members extracted from three 1,000-year-old Peruvian mummies, estimated that the most recent common ancestor of the ''M. tuberculosis'' complex lived only 4,000 – 6,000 years ago. The ''M. tuberculosis'' evolutionary rate estimated by the Bos et al. study is also supported by a study on Lineage 4 relying on genomic aDNA sequences from Hungarian mummies more than 200 years old. In total, the evidence thus favors this more recent estimate of the age of the MTBC most recent common ancestor, and thus that the global evolution and dispersal of ''M. tuberculosis'' has occurred over the last 4,000–6,000 years.

Among the seven recognized lineages of ''M. tuberculosis'', only two are truly global in their distribution: Lineages 2 and 4. Among these, Lineage 4 is the most well dispersed, and almost totally dominates in the Americas. Lineage 4 was shown to have evolved in or in the vicinity of Europe, and to have spread globally with Europeans starting around the 13th century. This study also found that Lineage 4 tuberculosis spread to the Americas shortly after the European discovery of the continent in 1492, and suggests that this represented the first introduction of human TB on the continent (although animal strains have been found in human remains predating Columbus. Similarly, Lineage 4 was found to have spread from Europe to Africa during the Age of Discovery, starting in the early 15th century.

It has been suggested that ancestral mycobacteria may have infected early hominids in East Africa as early as three million years ago. Even though the MRCA of extant M. tuberculosis seems to have existed as recently as 4,000-6,000 years ago, this does not necessarily suggest that TB did not exist prior to that, it merely means that all ''M. tuberculosis'' strains circulating today can be traced back to a common ancestor that lived at that point in time.''M. tuberculosis'', then known as the "tubercle bacillus", was first described on 24 March 1882 by Robert Koch, who subsequently received the Nobel Prize in Physiology or Medicine for this discovery in 1905; the bacterium is also known as "Koch's bacillus".

''M. tuberculosis'' has existed throughout history, but the name has changed frequently over time. In 1720, though, the history of tuberculosis started to take shape into what is known of it today; as the physician Benjamin Marten described in his ''A Theory of Consumption'', tuberculosis may be caused by small living creatures transmitted through the air to other patients. This airborne disease is the deadliest infectious disease worldwide, affecting nearly 2 billion people throughout the world currently. ''M. tuberculosi''s is easily passed through the air by sneezing, coughing, or simply talking. A contaminated droplet can infect any person and they can become contaminated with ''M. tuberculosis''. They thus become part of the 1.8 billion people worldwide who are currently struggling with this disease.

Cultural

''M. tuberculosis'' can be grown in the laboratory. Compared to other commonly studied bacteria, ''M. tuberculosis'' has a remarkably slow growth rate, doubling roughly once per day. Commonly used media include liquids such as Middlebrook 7H9 or 7H12, egg-based solid media such as Lowenstein-Jensen, and solid agar-based such as Middlebrook 7H11 or 7H10. Visible colonies require several weeks to grow on agar plates. It is distinguished from other mycobacteria by its production of catalase and niacin. Other tests to confirm its identity include gene probes and MALDI-TOF.