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REVIEW: Rpf Proteins Are the Factors of Reactivation of the Dormant Forms of Actinobacteria

V. D. Nikitushkin*, G. R. Demina, and A. S. Kaprelyants

Bach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology” of the Russian Academy of Sciences, 119071 Moscow, Russia; E-mail: vadimchemist@gmail.com

* To whom correspondence should be addressed.

Received June 10, 2016; Revision received September 20, 2016
As the response to unfavorable growth conditions, nonsporulating mycobacteria transform into the dormant state with the concomitant formation of the specialized dormant forms characterized by low metabolic activity and resistance to antibiotics. Such dormant cells can be reactivated under the influence of several factors including proteins of Rpf (Resuscitation promoting factor) family, which possess peptidoglycan hydrolase activity and were considered to belong to the group of the autocrine growth factors of the bacteria. Remarkable interest toward Rpf family is determined by its participation in resuscitation of the dormant forms of Mycobacterium tuberculosis, what in turn is the key element in resuscitation of the latent tuberculosis – an infectious disease that affects one third of the World’s population. Experiments with Rpf mutant forms and with strains deleted in these proteins revealed a relationship between the enzymatic activity of this protein and its ability to resuscitate mycobacteria both in vitro and in vivo. This review discusses possible mechanisms of Rpf action including those related to possible participation of the products of mycobacterial Rpf-mediated cell wall hydrolysis (muropeptides) as signaling molecules. The unique ability of Rpf proteins to resuscitate the dormant forms of mycobacteria and to stimulate their proliferation would allow these proteins to occupy their niche in medicine – in diagnostics and in creation of antituberculosis subunit vaccines.
KEY WORDS: Resuscitation promoting factor (Rpf), actinobacteria, dormancy, tuberculosis, lytic enzymes, bacterial cell wall, muropeptides, MALDI, vaccines, diagnostics

DOI: 10.1134/S0006297916130095