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Article

Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates

1
Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore 54590, Pakistan
2
Department of Bioscience and Biotechnology, The University of Suwon, Hwaseong, Gyeonggido 18323, Korea
3
National Leading Research Laboratory, Department of Biological Sciences, Myongji University, 116 Myongjiro, Yongin, Gyeonggido 17058, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Michaela Wenzel
Pharmaceuticals 2021, 14(5), 420; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050420
Received: 5 April 2021 / Revised: 15 April 2021 / Accepted: 25 April 2021 / Published: 1 May 2021
(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)
β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards β-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the mecA gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin. View Full-Text
Keywords: mutation; mecA; methicillin-resistant Staphylococcus aureus; allosteric site; PBP2a mutation; mecA; methicillin-resistant Staphylococcus aureus; allosteric site; PBP2a
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MDPI and ACS Style

Ali, T.; Basit, A.; Karim, A.M.; Lee, J.-H.; Jeon, J.-H.; Rehman, S.u.; Lee, S.-H. Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates. Pharmaceuticals 2021, 14, 420. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050420

AMA Style

Ali T, Basit A, Karim AM, Lee J-H, Jeon J-H, Rehman Su, Lee S-H. Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates. Pharmaceuticals. 2021; 14(5):420. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050420

Chicago/Turabian Style

Ali, Tanveer, Abdul Basit, Asad M. Karim, Jung-Hun Lee, Jeong-Ho Jeon, Shafiq u. Rehman, and Sang-Hee Lee. 2021. "Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates" Pharmaceuticals 14, no. 5: 420. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050420

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