Phage delivered CRISPR-Cas system to combat multidrug-resistant pathogens in gut microbiome
Arijit Nath, Rahul Bhattacharjee, Aditya Nandi, Adrija Sinha, Sulagna Kar, Nikita Manoharan, Shirsajit Mitra, Abhik Mojumdar, Pritam Kumar Panda, Swadheena Patro, Ateet Dutt, Rajeev Ahuja, Suresh K. Verma, Mrutyunjay Suar
Abstract
The Host-microbiome interactions that exist inside the gut microbiota operate in a synergistic and abnormal manner. Additionally, the normal homeostasis and functioning of gut microbiota are frequently disrupted by the intervention of Multi-Drug Resistant (MDR) pathogens. CRISPR-Cas (CRISPR-associated protein with clustered regularly interspersed short palindromic repeats) recognized as a prokaryotic immune system has emerged as an effective genome-editing tool to edit and delete specific microbial genes for the expulsion of bacteria through bactericidal action. In this review, we demonstrate many functioning CRISPR-Cas systems against the anti-microbial resistance of multiple pathogens, which infiltrate the gastrointestinal tract. Moreover, we discuss the advancement in the development of a phage-delivered CRISPR-Cas system for killing a gut MDR pathogen. We also discuss a combinatorial approach to use bacteriophage as a delivery system for the CRISPR-Cas gene for targeting a pathogenic community in the gut microbiome to resensitize the drug sensitivity. Finally, we discuss engineered phage as a plausible potential option for the CRISPR-Cas system for pathogenic killing and improvement of the efficacy of the system.