Drug efflux transporters in Staphylococcus pseudintermedius: in silico prediction and characterization of resistance.

Autor:	Rampacci E; Department of Veterinary Medicine, University of Perugia, via San Costanzo 4, Perugia 06126, Italy., Felicetti T; Department of Pharmaceutical Sciences, University of Perugia, via del Liceo 1, Perugia 06123, Italy., Pietrella D; Department of Medicine and Surgery, University of Perugia, via Gambuli 1, Perugia 06156, Italy., Sabatini S; Department of Pharmaceutical Sciences, University of Perugia, via del Liceo 1, Perugia 06123, Italy., Passamonti F; Department of Veterinary Medicine, University of Perugia, via San Costanzo 4, Perugia 06126, Italy.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2022 Nov 28; Vol. 77 (12), pp. 3283-3290.
DOI:	10.1093/jac/dkac314
Abstrakt:	Objectives: To perform an in silico prediction of drug efflux pumps (EPs) in Staphylococcus pseudintermedius and investigate their role in conferring resistance to antibiotic and biocidal agents and biofilm formation. Methods: A S. pseudintermedius efflux mutant was obtained by stimulating an isogenic line (ATCC 49444) with increasing concentrations of an efflux system substrate. Changes in antimicrobial susceptibility and biofilm-forming capability were evaluated in the presence/absence of the EP inhibitors (EPIs) thioridazine and reserpine and the efflux activity was assayed by fluorometry. Homologues of EPs of Staphylococcus aureus and Staphylococcus epidermidis were searched by exploratory GenBank investigations. Gene expression analyses and sequencing were then conducted on selected genes. Results: Susceptibility to chlorhexidine, gentamicin and ciprofloxacin, but not enrofloxacin, was affected by the increased efflux and it was variably restored by the EPIs. The efflux mutant showed much greater biofilm formation that the original strain, which was significantly inhibited by thioridazine and reserpine at MIC/2. A high expression of norA, which was mgrA-independent, was found in the S. pseudintermedius efflux mutant, apparently regulated by an 11 bp deletion in its promoter region, whilst lmrB was transitorily overexpressed. icaA, which encodes the polysaccharide intercellular adhesin forming the extracellular matrix of staphylococcal biofilm, was also up-regulated. Conclusions: EPs, particularly NorA, are supposed to have complex involvement in multiple stages of resistance development. Overexpression of EPs appears to be correlated with a remarkable increase of S. pseudintermedius biofilm production; however, the regulatory mechanisms remain to be explored. (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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