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Article

Proteomic Comparison of Ivermectin Sensitive and Resistant Staphylococcus aureus Clinical Isolates Reveals Key Efflux Pumps as Possible Resistance Determinants

1
Department of Animal Sciences, McGill University, Sainte-Anne-de-Bellevue, Quebec, QC H9X 3V9, Canada
2
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
3
Department of Pathobiology, Riphah University, Lahore 54500, Pakistan
4
Department of Bioresource Engineering, McGill University, Sainte-Anne-de-Bellevue, Montreal, QC H9X 3V9, Canada
5
Biomedicinska Centrum, Institutionen för Medicinsk Biokemi och Mikrobiologi, Uppsala Universitet, 751 23 Uppsala, Sweden
6
School of Veterinary Medicine, University of Surrey, Guildford GU2 7AL, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Khondaker Miraz Rahman
Antibiotics 2022, 11(6), 759; https://doi.org/10.3390/antibiotics11060759
Received: 19 April 2022 / Revised: 26 May 2022 / Accepted: 1 June 2022 / Published: 2 June 2022
Ivermectin (IVM) is a versatile drug used against many microorganisms. Staphylococcus aureus is one of the most devastating microorganisms. IVM sensitive and resistant S. aureus strains were recently reported. However, the underlying molecular mechanisms of resistance are unknown. Clinical isolates of S. aureus were used for determination of the sensitivities against IVM by growth curve analysis and time-kill kinetics. Then, proteomic, and biochemical approaches were applied to investigate the possible mechanisms of resistance. Proteomic results showed a total of 1849 proteins in the dataset for both strains, 425 unique proteins in strain O9 (IVM sensitive), and 354 unique proteins in strain O20 (IVM resistant). Eight proteins with transport functions were differentially expressed in the IVM resistant strain. Among them, three efflux pumps (mepA, emrB, and swrC) were confirmed by qPCR. The IVM resistant S. aureus may overexpress these proteins as a key resistance determinant. Further experiments are required to confirm the exact mechanistic relationship. Nevertheless, the possibility of blocking these transporters to reverse or delay the onset of resistance and reduce selection pressure is potentially appealing. View Full-Text
Keywords: ivermectin; Staphylococcus aureus; proteomics; genomics; efflux pumps; virulence factor ivermectin; Staphylococcus aureus; proteomics; genomics; efflux pumps; virulence factor
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MDPI and ACS Style

Ashraf, S.; Parrine, D.; Bilal, M.; Chaudhry, U.; Lefsrud, M.; Zhao, X. Proteomic Comparison of Ivermectin Sensitive and Resistant Staphylococcus aureus Clinical Isolates Reveals Key Efflux Pumps as Possible Resistance Determinants. Antibiotics 2022, 11, 759. https://doi.org/10.3390/antibiotics11060759

AMA Style

Ashraf S, Parrine D, Bilal M, Chaudhry U, Lefsrud M, Zhao X. Proteomic Comparison of Ivermectin Sensitive and Resistant Staphylococcus aureus Clinical Isolates Reveals Key Efflux Pumps as Possible Resistance Determinants. Antibiotics. 2022; 11(6):759. https://doi.org/10.3390/antibiotics11060759

Chicago/Turabian Style

Ashraf, Shoaib, Débora Parrine, Muhammad Bilal, Umer Chaudhry, Mark Lefsrud, and Xin Zhao. 2022. "Proteomic Comparison of Ivermectin Sensitive and Resistant Staphylococcus aureus Clinical Isolates Reveals Key Efflux Pumps as Possible Resistance Determinants" Antibiotics 11, no. 6: 759. https://doi.org/10.3390/antibiotics11060759

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