PmrA Mutations in Drug-Resistant <i>Acinetobacter baumannii</i> Affect Sensor Kinase-Response Regulator Interaction and Phosphotransfer.

ABSTRACT: Multi-drug resistance in Acinetobacter baumannii poses a significant human health threat. For multidrug-resistant pathogens, 'last line of defense' antibiotics like the polymyxins are implemented. Concerningly, polymyxin-resistance is evidenced in Acinetobacter baumannii and is mediated by the PmrAB two-component system. The response regulator PmrA upregulates pmrC, leading to lipooligosaccharide modifications that reduce polymyxin binding. Sequencing of A. baumannii resistant isolates has identified point mutations in the receiver domain of PmrA that correlate with increased resistance. To investigate functional impacts of these mutations, we characterized five PmrA mutations (D10N, M12I, I13M, G54E, and S119T) by assessing changes in PmrA DNA-binding affinity,

SUBMITTER: Jaimes FE 

PROVIDER: S-EPMC12654582 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature