Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, India
Title of the talk: Targeted Depletion of Campylobacter jejuni via Type Six Secretion System (T6SS) functionality in chickens
Abstract
Common gut pathogens are armed with several intrinsic mechanisms for subverting host defense, facilitating host pathogenicity, and enduring exposure to various environmental stressors; hence, their selective targeting is often challenging. To this end, several pathogenic gut microbiota utilize highly specialized secretion systems for self-survival, promoting disease progression and competitive advantages in the gut. Among them, the bacterial Type VI Secretion System (T6SS) is known for its versatile function and can secrete a range of effector molecules to modulate the intestinal microenvironment, attacking both prokaryotic and eukaryotic cells in a contact-dependent manner. Despite the competitive fitness advantage of the T6SS, its functionality can depend on the physio-chemical composition of the gut, such as pH, bile salt concentration, and other antimicrobial components. To understand how such stressors affect the activity and the ultimate infectivity of T6SS-harboring pathogens, we exploited microbial competition via the bacterial Type VI secretion system (T6SS) of Campylobacter jejuni (C. jejuni), a common gut commensal of chickens. Employing a T6SS-positive-C. jejuni and an isogenic mutant of the hemolysin-coregulated protein (hcp), a major effector of T6SS, we could trace a marked intracellular influx of bile salts followed by a significant reduction in C. jejuni, suggesting that T6SS-mediated bile salt entry can enhance intracellular oxidative stress, affecting C. jejuni viability. We further investigated whether the T6SS activity in the presence of prey bacteria perturbs in vivo colonization of C. jejuni. Using chickens as primary hosts of C. jejuni and non-pathogenic E. coli as prey, we showed a noticeable reduction in the cecal load of C. jejuni with orally administered bile salt solution. Analysis of local antibody responses and pro-inflammatory gene expression showed a reduced risk of tissue damage, indicating that T6SS activity in the complex gut environment can be utilized as a possible measure to clear persistent colonization of C. jejuni in chickens.
Biography
Amirul Mallick completed his Ph.D. in Biotechnology at the age of 27 years from Aligarh Muslim University, India, and received his postdoctoral training from Ontario Veterinary College, University of Guelph (Canada) and Sunnybrook Research Institute, University of Toronto (Canada) from 2008 to 2014. Currently, he is an Associate Professor at the Dept. of Biological Sciences, Indian Institute of Science Education and Research Kolkata (IISER-K), a premier academic cum research institute in India. He has published over 50 peer-reviewed research articles in highly regarded journals and has been an editorial board member of Gut Pathogens (Springer Nature) and The Microbe (ELSEVIER) journals. The overarching theme of his research is understanding the molecular mechanism of “host-pathogen and microbes-microbes interaction” to address the “One Health” issues. Considering the global concerns of emerging infectious and zoonotic diseases (EIZDs), his research group is actively working to advance the current concept of biotherapeutics and immuno-prophylaxis modalities for diseases of global importance, such as Type A Influenza virus and important gut pathogens.