BIOMEDICAL JOURNAL OF PIROGOV RNRMU (MOSCOW, RUSSIA)
Serine/threonine protein kinases of bacteria are potential targets for regulation of human microbiota composition
Serine/threonine protein kinases (STPKs) of bacteria are involved in signal transduction, cell growth and division, biofilm formation and virulence regulation. They are found in both pathogenic microbes and symbiotic residents of the human microbiota. Previously we proposed a classification scheme for STPKs of gram-positive bacteria based on the signature sequence of 9 amino acid residues in the ATP-binding pocket. Accordingly, protein kinases and bacterial species that contained those kinases were divided into 20 groups. We hypothesized that STPKs with identical signatures would interact with the same low-molecular-weight compounds that could be used as selective inhibitors of STPK to suppress growth and virulence of certain residents of the human gut microbiota (GM). GM represented by over 400 bacterial species is critical in maintaining homeostasis in the human body. In healthy individuals GT composition is balanced in terms of genera/species abundance. Shifts in the GT composition are thought to trigger pathology. In this connection various approaches are being developed to regulating the composition of the human microbiota. This article proposes the use of bacterial STPK inhibitors as “gentle” therapeutic agents for correcting taxonomic imbalances of GM triggered by non- infectious diseases and reducing virulence of pathogenic microbes with minimal impact on human protein kinases.
Keywords: classification, gut microbiota, serine-threonine protein kinases, selective inhibitors, gram-positive bacteria