Resuscitating Mycobacterium tuberculosis

Mycobacterium tuberculosis Mycobacterium tuberculosis can persist in the host for decades after infection before reactivating to cause disease. The bacterial and host factors that contribute towards latent TB infection and reactivation disease have long remained enigmatic. However, there is considerable circumstantial evidence to suggest that the persisting organisms may include bacteria in physiological states that are characterized by impaired culturability (i.e. colony-forming ability). These observations suggest a plausible link between an intrinsic microbiological property of M. tuberculosis the ability to enter into a state of dormancy from which culturability can be restored and the clinically defined phenomenon of latent infection.
M. tuberculosis contains five resuscitation-promoting factor (Rpf)-like proteins, RpfA-E, that are implicated in resuscitation of this organism from dormancy via a mechanism involving hydrolysis of the peptidoglycan by Rpfs and partnering proteins. In this study, the rpfA-E genes were shown to be collectively dispensable for growth of the organism in broth culture. The defect in resuscitation of multiple mutants from a non-culturable state induced by starvation under anoxia was reversed by genetic complementation or addition of culture filtrate from wild-type organisms confirming that the phenotype was associated with rpf-like gene loss and that the non-culturable cells of the mutant strains were viable. Other phenotypes uncovered by mutagenesis revealed a functional differentiation within this protein family.
Researchers have yet to unravel the complexities which underpin the in vivo phenotypes and relate them to the various in vitro phenotypes associated with rpf-like gene loss. The fact that some Rpfs interact with other proteins in the cell to form protein complexes that may cleave distinct forms of peptidoglycan further adds to the complexity of Rpf function and regulation. However, the collection of mutant strains reported in this and earlier studies are an important resource for future biochemical, microbiological and physiological studies on this fascinating family of proteins.

The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Molecular Microbiology, 21 Dec 2007

Tags: , , , , , , ,

3 Comments

  • Hi,

    I have wanted to express my admiration for your blog for some time now. The New Year seems to be a good occasion, and so does you latest posting on M. tuberculosis and its quirky and bothersome yen for being latent. As a consequence, members of this genus plus the rickettsiae that cause recrudescent typhus are the only bacteria I am aware of that may qualify as endosymbionts of vertebrates. It seems plausible that the latent forms reside intracellularly. In macrophages?

  • ajcann says:

    Thanks very much for your comment. I’m not an expert on M.tb, but what I do know about it suggests that your hunch about macrophages is quite likely to be correct!

    Anyone?

  • Judy Goforth Parker says:

    I hate to say this, but TB is my favorite disease. I teach community health nursing, and the students think that I am crazy. I am going to show them your picture.