TARGETING ESSENTIAL GENETIC PATHWAYS IN MULTI-DRUG-RESISTANT MRSA AND A. BAUMANNII

Abstract

Global spread of infections resistant to various medications including Methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii are a consistent danger to health of people. Complex genetic, metabolic and regulatory schemes allow these organisms to survive under tough conditions, evade immune system of their host and endure numerous antibiotic regimens. The cell envelope plays a crucial role in ensuring bacteria remain alive since it maintains the structure of the cell intact, as well as giving it a way of contacting the host. Lipid A in the outer membrane has lipopolysaccharide in Gram-negative bacteria such as the A. baumannii-bacterium. Lipid A requires the use of the enzymes lpxA, lpxC, and lpxD, and is required to enhance the stability of the membrane and its virulence. The integrity of the wall in MRSA is determined by the presence of wall teichoic acids produced by tarO, tarS, and tarM. These acids play a role in the production of peptidoglycan and resistance of the cell wall against 3 beta-lactam. The efflux pumps are regulated by genes such as AdeRS and MarR-based systems and through which bacteria become resistant to most drugs by actively exporting antibiotics. Virulence, biofilm formation and toxin production levels in MRSA and A. baumannii are regulated through quorum sensing systems such as agr and AbaI/AbaR respectively. CRISPR to target the particular genes to eliminate resistance determinants and phages to express the CRISPR system are among the new methods to treat the disease as well as artificial intelligence in finding a new drug through a synthesis of structure-based design and multi-omics data. The effectiveness and the ability to delay resistance development can be enhanced by the combination therapy plans, which involve the multiple pathways simultaneously. Despite these advances, major issues do persist, such as high rates of mutation, receiving the drug facing barriers in Gram-negative bacteria, toxicity, and rapid adaptive resistance. The contributions of looking at bacterial structural elements, regulatory networks, metabolic pathways, and virulence mechanisms represents an important shift in perspectives of how traditional antibiotics to precision antimicrobial therapy. Integrating pioneer genetic, metabolic, and computational approaches would assist us to access multidrug resistance, reduce selective pressures and improve clinical outcomes in long-term infections by bacteria that are exceedingly difficult to sanitary and persist within the body.