Electroporation of pLI50 harboring qacA or qacB increases chlorhexidine minimal inhibitory concentrations in transformed Staphylococcus aureus strain RN4220.

Authors

Kai-Hsiang Lin, Chieh-Chen Huang, Cheng-Mao Ho

Published in

Scientific reports. Jun 18, 2026. Epub Jun 18, 2026.

Abstract

QacA and QacB are staphylococcal multidrug efflux proteins that share high sequence homology, differing by only six to seven amino acids. While the prevalence of these genes among clinical isolates can exceed 70% in certain regions, and qacA is well-documented to elevate chlorhexidine minimal inhibitory concentrations (MICs), the specific contribution of qacB to chlorhexidine tolerance remains incompletely defined. To investigate these differences, in silico structural analyses were performed using UCSF ChimeraX. Sequence data from NCBI were mapped onto the experimental 3.80 Å cryo-EM structure of QacA (PDB ID: 7Y58) to compare global and local conformational and electrostatic properties. Phenotypically, the pLI50 plasmid carrying either qacA or qacB was electroporated into Staphylococcus aureus strain RN4220. Chlorhexidine MICs were subsequently determined using agar dilution assays. Global in silico modeling demonstrated that the amino acid substitutions distinguishing QacB from QacA did not alter the backbone conformation, hydrogen bond counts, solvent-accessible surface area, or overall Coulombic surface potential. However, local analyses identified distinct microenvironmental perturbations attributable to the physicochemical differences of the substituted residues. Phenotypically, the introduction of qacA into S. aureus RN4220 reproducibly increased chlorhexidine MICs from 1 µg/mL to 4 µg/mL in 96% (48/50) of independent assays (adjusted OR > 999; P < 0.001). Conversely, the presence of qacB significantly increased MICs from 1 µg/mL to 2 µg/mL in 90% (45/50) of analogous assays, demonstrating a distinct but less pronounced elevation in tolerance (adjusted OR = 81.0; P = 0.0013). Both qacA and qacB contribute to increased chlorhexidine MICs in S. aureus RN4220 under the conditions tested. Given the high prevalence of these genes among clinical isolates and the widespread use of chlorhexidine in infection prevention, these findings support continued surveillance and further mechanistic studies to assess clinical and infection-control implications.

PMID:
42315725
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.

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