UNDERSTANDING MULTIDRUG RESISTANCE TRANSMISSION AND THE ACTION OF POLYIMIDAZOLIUM DERIVATIVES IN COMBATING MDR INFECTION IN GRAM-NEGATIVES

Abstract

The emergence of antimicrobial resistance (AMR) presents a challenge to treatment of bacterial infections. Transmissible plasmids pKPC2 and pNDM1 are predominant among Singapore's carbapenem-resistant Enterobacterales isolates. pKPC2 is a novel IncP plasmid displaying superior transferability compared to pNDM1 among Enterobacterales isolates and is very stable in vitro. I discovered that the presence of capsule in hypervirulent Klebsiella pneumoniae strains decreased their transfer in vitro, but not in murine gut. In parallel, we also examined a novel cationic antimicrobial (OIM1-6) and showed that it has an intracellular mode of action that relies on membrane potential for entry. Once inside, OIM1-6 binds to DNA and induces DNA damage in E. coli. Collectively, these studies reveal the presence of highly evolved AMR plasmids in hospitals that require increased surveillance, and aid in the development of novel antimicrobials to bolster our readiness in combating AMR.