Interruption of AbaI/AbaR quorum sensing signals: A potential approach against multidrug-resistant Acinetobacter baumannii

Background: Acinetobacter baumannii is a multidrug-resistant opportunistic pathogen frequently associated with ventilator-related and other hospital-acquired infections. Its pathogenicity is largely driven by several virulence factors and associated genes. Its ability to survive under harsh conditions and resist multiple antibiotics is strongly governed by quorum sensing (QS), a cell-to-cell communication mechanism that coordinates gene expression in response to population density. The QS system in A. baumannii primarily relies on the AbaI/AbaR circuit, where AbaI synthesizes acyl-homoserine lactones (AHLs) that subsequently activates virulence-associated genes. An indole-mediated QS system also regulates stress responses, and together these signaling networks coordinate gene expression. Therefore, targeting, the QS system represents a promising anti-virulence therapeutics strategy. Understanding QS mechanisms and exploring potent quorum- sensing inhibitors hold significant potential for developing novel therapeutics against A. baumannii infections. This review aims to elucidate the role of AbaI/AbaR QS system in regulating virulence, biofilm formation, and antibiotic resistance in A. baumannii, and to evaluate current quorum-sensing inhibitor-based approaches as potential anti-virulence therapies against multidrug-resistant infections.