Life Sciences & Biotechnology
Title : | Response against starvation as the determinant of infection by pathogenic bacteria and the target for the therapy |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Ritesh Ranjan Pal, Indian Association For The Cultivation Of Science, West Bengal |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | riteshrpal@gmail.com |
Equipments : | Chemidoc
Cryocan |
Details
Executive Summary : | Enteropathogenic Escherichia coli (EPEC), is an important pediatric diarrheal pathogen. It is a typical attaching and effacing enteric pathogen, which resides in the challenging niche of the host intestine throughout the course of infection. EPEC colonizes this niche in a process that is dependent on a type III secretion system, through which protein effectors are translocated into the host. In this niche, EPEC competes for nutrients with both the intestinal epithelial cells and the vast enteric microbiota. Our recent publication also suggests that EPEC extract nutrients from host cells while infecting it using a novel conduit named membranous nanotubes with conserved inner membrane export apparatus (CORE). Thus, EPEC most likely faces starvation and execute stringent response with the gut of the human host. The stringent response is characterized by the accumulation of the (p)ppGpp [guanosine 3′-diphosphate 5′-triphosphate (pppGpp) and guanosine 3’,5’- bis(diphosphate) (ppGpp)] in the E. coli cell. (p)ppGpp metabolism is regulated by RelA and SpoT. Thus, deletion of genes encoding these two proteins leads to the (p)ppGpp0 strains of E. coli that cannot synthesize (p)ppGpp. It is well known in several bacteria that (p)ppGpp also regulates virulence gene expression. It is also found for EPEC that the attachment of EPEC to the host and nanotube formation is somehow related to the starvation or stringent response. In this proposed research, we will try to elucidate the comprehensive role of stringent response in infection EPEC. We will try to define the role of (p)ppGpp in the formation of nanotubes in relation to their infection capability. As both stringent response and nanotube formation have some conserved themes for bacteria, it will also be interesting to verify their effects on other pathogenic bacteria like Vibrio cholerae, Salmonella, and helicobacter pylori. Moreover, attempts will be taken to identify a broad spectrum therapy against bacterial pathogen targeting those conserved phenomena. |
Total Budget (INR): | 29,95,400 |
Organizations involved