Selection and validation of EPI for overcoming resistance of M morganii to colistin A genome to drug approach for repurposing

Abstract

Morganella morganii, a non-negligent opportunistic pathogen of the family Enterobacteriaceae, has been enlisted recently in the global priority pathogens by WHO for its swift propensity to acquire drug-resistant genes, engendering enhanced death rates. A combination of diverse antimicrobials could be recycled to overcome the ongoing acquisition of resistance mechanisms by M. morganii. M. morganii, inherently resistant to colistin, can cause various clinical and community-acquired infections. The strains collected from critical departments of tertiary care hospitals were identified and tested for antimicrobial susceptibility by the VITEK 2 automated system. The 16S rRNA sequencing was used to reconfirm the species identification and named UM169, UM869, and UM573 with accession numbers ON533443, ON533444 and ON533445, respectively. According to the antibiogram profiling, UM869 shows resistance to several antibiotics, according to the VITEK 2 analysis. The high resistance profiling of UM869 compelled us to undergo the whole genome sequencing to investigate the virulence factors, drug resistance mechanisms, predicted functional pathways and comparative genomic analysis of 79 published M. morganii genomes, including our strain UM869 (accession number GCA_025398975). The resistance to major antibiotic classes in the core orthologs of these genomes is manifested through antibiotic target alteration (PBP3, gyrB) and antibiotic efflux (AcrB, kpnH, rsmA, CRP), which includes our strain. Further, our strain harboured 65 genes associated with 30 virulence factors, which include efflux pump, hemolysin, urease, adherence, toxin, and endotoxin. A similar resistance profile was also detected in the core ortholog sequences, although their number is 28 and 36, respectively. Detection of high genomic similarity (ANI-98.37%) among the genomes might be due to the dissemination of genes into adjoining countries. The genes predicted for super pathways in all core orthologs sequences were transporters (468), two-component systems (148),