M. tuberculosis persistence, latency, and drug tolerance

Gómez, James; McKinney, John D.

doi:10.1016/j.tube.2003.08.003

Cited by 485 publications

(433 citation statements)

References 72 publications

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“…Because TA loci encoding mRNases and other types of inhibitors of translation are highly abundant in bacteria and archaea, our observations raise the possibility that the mechanism of persister generation revealed here is more general. Mycobacterium tuberculosis, well known for its long-term persistence in the human body (52)(53)(54), has at least 88 TA loci, the majority of which encode inhibitors of translation (55,56). It is now important to learn if TA loci are also central to the persistence of pathogenic bacteria.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Bacterial persistence by RNA endonucleases

Maisonneuve

Shakespeare

Jørgensen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

459

557

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Bacteria form persisters, individual cells that are highly tolerant to different types of antibiotics. Persister cells are genetically identical to nontolerant kin but have entered a dormant state in which they are recalcitrant to the killing activity of the antibiotics. The molecular mechanisms underlying bacterial persistence are unknown. Here, we show that the ubiquitous Lon (Long Form Filament) protease and mRNA endonucleases (mRNases) encoded by toxin-antitoxin (TA) loci are required for persistence in Escherichia coli . Successive deletion of the 10 mRNase-encoding TA loci of E . coli progressively reduced the level of persisters, showing that persistence is a phenotype common to TA loci. In all cases tested, the antitoxins, which control the activities of the mRNases, are Lon substrates. Consistently, cells lacking lon generated a highly reduced level of persisters. Moreover, Lon overproduction dramatically increased the levels of persisters in wild-type cells but not in cells lacking the 10 mRNases. These results support a simple model according to which mRNases encoded by TA loci are activated in a small fraction of growing cells by Lon-mediated degradation of the antitoxins. Activation of the mRNases, in turn, inhibits global cellular translation, and thereby induces dormancy and persistence. Many pathogenic bacteria known to enter dormant states have a plethora of TA genes. Therefore, in the future, the discoveries described here may lead to a mechanistic understanding of the persistence phenomenon in pathogenic bacteria.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Bacterial persistence by RNA endonucleases

Maisonneuve

Shakespeare

Jørgensen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

459

557

View full text Add to dashboard Cite

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“…Clinically, latency is defined as the persistence of a tuberculous lesion with viable mycobacteria in a host without symptoms [20]. Unfortunately, proper methods for diagnosis of latent tuberculosis that also allow to distinguish it from chronic tuberculosis do not exist for humans and animals.…”

Section: Latencymentioning

confidence: 99%

Bovine tuberculosis as a model for human tuberculosis: advantages over small animal models

Rhijn

Godfroid

Michel

et al. 2008

Microbes and Infection

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“…tuberculosis has been considered the world's most successful pathogen and this is largely due to the ability of the bacillum to persist in host tissues, where drugs that are rapidly bactericidal in vitro require prolonged administration to achieve comparable effects (Hingley-Wilson et al 2003, Gomez & McKinney 2004. Hence more effective and less toxic anti-tubercular agents are urgently needed to shorten the duration of current treatment, improve the treatment of MDR-TB, and to provide effective treatment of latent tuberculosis infection (O'Brien & Nunn 2001).…”

Section: Tuberculosis (Tb)mentioning

confidence: 99%