Life Sciences & Biotechnology
Title : | Deciphering the enigmatic host-lysis mechanism of transposable phage Mu and its application towards the development of bacterial antimicrobial resistance (AMR) combating strategies |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Microbiology and Molecular Biology |
Principal Investigator : | Dr. Rudra Prasad Saha, Adamas University, West Bengal |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | rudraprasad.saha@adamasuniversity.ac.in |
Details
Executive Summary : | The human microbiome consists of microbes that outnumber human cells ten to one and can affect individual responses to drugs leading to adverse effects. Recent studies have shown that the human intestinal consumption of specific bacteriophages although efficiently reduces the targeted bacteria, also has minor disruption of some gut microbial communities. Analysis of the practically untapped repertoire of the bacteriophages in nature, especially the mutualistic relationship between the phage and the host, would help us to understand their behavior inside bacterial or animal hosts and enable us to design more effective phage therapy strategies to combat the onset of multidrug-resistant (MDR) bacterial strains. Little has been known about the ‘semi-essential’ (SE) region of transposable bacteriophage Mu as most of the SE region proteins do not have any known function or homologs in the present sequence databases, but these proteins are predicted to confer host-fitness attributes. There are sixteen SE region genes on the Mu genome, among these functions of kil, gam, gemA, and mor is known, and the rest twelve genes are of unknown nature, yet they are predicted to confer growth fitness to the host. On the other hand, another mystery in the Mu genome is its lysis proteins. Bacteriophage-mediated host-lysis is a common biological process. A detailed study of the bacteriophage lysis process and the proteins involved in this process will help researchers to discover new mechanisms of host-pathogen interaction, especially, their roles in pathogenic bacteria, which could be used to develop new drugs/therapeutics to kill multidrug-resistant bacteria. Our preliminary analysis suggests the presence of at least seven phage Mu proteins that involve in host lysis indicating the presence of a new lysis pathway functioning in Mu phage (including the presence of a single lysis protein that was never reported in a double-stranded DNA phage before). In the current project, we aim to illuminate the mystery of Mu phage – the discovery of phage Mu host-lysis genes and its mechanism of action. In addition, Mu-like phages that are found in both gram-positive and gram-negative bacteria will be analyzed to classify the variety of lysis genes present in them. Finally, we will also find out whether Phage Mu or its lysis proteins can be used as antimicrobials. Bacteriophages are the main driving factor for the host evolution and understanding the ‘phage-bacteria’ synergy would not only provide us with novel insights into their relationship but also advance the development of phage-derived alternative strategies for the control of antimicrobial-resistant strains of bacteria. |
Co-PI: | Dr. Arijit Bhattacharya, Adamas University, Kolkata,West Bengal, Dr. Kuntal Pal, Adamas University, Kolkata,West Bengal (700126) |
Total Budget (INR): | 57,61,800 |
Organizations involved