Resuscitation-promoting factors as lytic enzymes for bacterial growth and signaling.
Resuscitation-promoting factor (Rpf) is a muralytic enzyme that increases the culturability of dormant bacteria. Recently, considerable progress has been made in understanding the structure, function and physiological role of Rpfs in different organisms, most notably the major human pathogen, Mycobacterium tuberculosis, which encodes multiple rpf-like genes. A key unresolved question, however, concerns the relationship between the predicted biochemical activity of Rpfs - cleavage of the beta-1,4 glycosidic bond in the glycan backbone of peptidoglycan - and their effect on culturability. In M. tuberculosis, the interaction between RpfB and the d,l-endopeptidase, Rpf interacting protein A (RipA), enables these proteins to synergistically degrade peptidoglycan to facilitate growth. Furthermore, the combined action of Rpfs with RipA and other peptidoglycan hydrolases might produce muropeptides that could exert diverse biological effects through host and/or bacterial signaling, the latter involving serine/threonine protein kinases. Here, we explore these possibilities in the context of the structure and composition of mycobacterial peptidoglycan. Clearly, a deeper understanding of the role of Rpfs and associated peptidoglycan remodeling enzymes in bacterial growth and culturability is necessary to establish the significance of dormancy and resuscitation in diseases such as tuberculosis, which are associated with long-term persistence of viable bacterial populations recalcitrant to antibiotic and immune clearance.
MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, School of Pathology, University of the Witwatersrand and the National Health Laboratory Service, Johannesburg, South Africa. bavesh.kana@nhls.ac.za
Bavesh Davandra
BD
Kana
Valerie
V
Mizrahi
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism*; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
D001426:Bacterial Proteins; D003470:Culture Media; D016207:Cytokines; D010457:Peptidoglycan; C113704:resuscitation-promoting factor, bacteria; D009238:N-Acetylmuramoyl-L-alanine Amidase