Research Projects

Rho, an essential protein in Gram-negative bacteria and M. tuberculosis, is a potential drug target in enteropathogenic E. coli, S. flexneri, S. enterica, and M. tuberculosis. The antibiotic bicyclomycin (BCM) inactivates Rho, leading to genome-wide pervasive transcription and the expression of laterally acquired toxic prophage genes. This results in DNA damage, spontaneous mutations, and death of the bacteria. Rho function is linked to pH homeostasis in bacteria, with suboptimal and excess Rho function causing alkalinity or acidity. Inhibition of Rho by BCM also raises cytoplasmic pH. The mechanism for Rho-linked pH fluctuation and its connection with pH homeostasis pathways will be explored. H-NS, an abundant nucleoid protein, also suppresses lateral, pathogenic island, and acid-resistant gene expression. Rho and H-NS share an overlapping function to suppress laterally-acquired and virulent factors encoding genes. However, little is known about the mechanism of this influence and its evolutionary significance. The proposal aims to decipher a valid connection between Rho and H-NS functions by examining pH fluctuation and H-NS function. Pathogens like E. coli, S. flexneri, and S. enterica encounter extreme pH conditions while infecting and colonizing the gut. Rho-dependent pH alteration coupled with variations in Rho and H-NS functions can allow evolutionary fitness to pathogens by regulating toxic and virulent gene expression. The proposed approach will unravel a survival strategy of bacterial pathogens and help devise human strategies to defeat them.