Resuscitation-promoting Factors (Rpf): In Search of Inhibitors

Arseny      S. Kaprelyants; Galina      V. Mukamolova; Alessia      Ruggiero; Vadim      A. Makarov; Galina      R. Demina; Margarita      O. Shleeva; Vasilii      D. Potapov; Pavel      A. Shramko

Abstract

Resuscitation promoting factors (Rpf) are a family of proteins secreted by actively growing actinobacteria, including Mycobacterium tuberculosis. Experimental evidence suggests that Rpfs play a distinct role in bacterial resuscitation and re-growth as well as reactivation of chronic tuberculosis in mice. The striking similarity of the Rpfs structure to cell wall hydrolysing enzymes has provided a basis for the development of novel low molecular weight inhibitors of Rpfs activity. In particular, recently characterised nitrophenylthiocyanate compounds could be considered as a promising scaffold for generation of therapeutic agents targeting reactivation of latent tuberculosis. This review describes recent progress in understanding of molecular mechanisms of Rpf biological activity.

Keywords: Inhibitors, latency, nitrophenylthiocyanates, resuscitation, Rpf, tuberculosis, Mycobacterium tuberculosis, cell wall hydrolysing enzymes, therapeutic agents, molecular mechanisms