PROTEIN KINASES, A CENTRAL HUB FOR SEVERAL CELLULAR RESPONSES INCLUDING ANTIMICROBIAL RESISTANCE: AN EMERGING PARADIGM IN Klebsiella SIGNALING

Abstract : On 30th April 2014, World Health Organization released its first global report on antibiotic resistance and stated the manifold crisis as serious threat to public health worldwide. Since last few decades a significant upsurge in multidrug resistance among Klebsiella pneumoniae strains has been a cause for serious concern among national and international health care settings, overall emphasizing the pressing need to identify novel treatment options and identify the molecular signatories behind antibiotic resistance, its emergence and persistence. The genome sequence of K. pneumoniae encodes several putative membrane proteins and signaling systems in its chromosome. Our initial studies on novel secondary transporters/efflux pumps, outer membrane proteins/porins and bacterial signaling systems (their interplay), have decoded their functions in regulating bacterial physiology, stress response, virulence and antimicrobial resistance. Though known as respiratory pathogen for decades, the implications of Ser/Thr phosphorylation in cellular physiology and drug resistance remained a neglected area of Klebsiella research. I will be discussing the biochemical and biological functions of idiosyncratic Ser/Thr protein kinase, a new paradigm of cellular signaling which has marked just the beginning and my future plan of work to get answers to few fundamental questions such as a) Understanding how bacteria communicate and exchange genetic information in order to sustain antibiotic assails? b) What molecular events allow the pathogen to manifest drug resistance? c) Does antibiotic trigger a mutagenic pathway that results in emergence of multidrug resistance? d) Which are the fundamental genetic mechanisms that facilitate the origin of drug resistance? We believe our study will greatly advance our present limited understanding on K. pneumoniae’s communication strategies and implications of this research can be envisioned in understanding the global Klebsiella signaling networks and its components, and such knowledge gained can be critical to combat K. pneumoniae illness as these enzymes have the potential to serve as novel targets for alternative antibiotic therapy.