Relative Contributions of Quinolone Resistance-Determining Region Mutations and Efflux Pump-Associated Mechanisms to Fluoroquinolone Resistance in Staphylococcus aureus Clinical Isolates and Their Associations with Virulence Gene Profiles.
8 affiliations
- 1Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Republic of Korea.
- 2Next-Generation Industrial Field-Based Specialist Program for Molecular Diagnostics, Brain Busan 21 Plus Project, Graduate School, Catholic University of Pusan, Busan 46252, Republic of Korea.
- 3Department of Clinical Laboratory Science, Hyejeon University, Hongseong 32244, Republic of Korea.
- 4Department of Forensic Science, Graduate School, Catholic University of Pusan, Busan 46252, Republic of Korea.
- 5Department of Laboratory Medicine, Konyang University Hospital, Daejeon 35365, Republic of Korea.
- 6Department of Research & Development, Q-Solutions, Changwon 51508, Republic of Korea.
- 7Division of Research & Development, Dream Dx Inc., Busan 48059, Republic of Korea.
- 8Department of Biomedical Laboratory Science, Masan University, Changwon 51217, Republic of Korea.
Abstract
Background: Fluoroquinolone resistance in methicillin-resistant Staphylococcus aureus (MRSA) involves multiple mechanisms, including quinolone resistance-determining region (QRDR) mutations and efflux pump activity. However, the relationship between these resistance mechanisms and virulence factors (VFs) remains unclear. This study investigated the relative contributions of QRDR mutations and carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-responsive mechanisms to fluoroquinolone resistance in MRSA and their associations with VF profiles. Methods: Sixty ciprofloxacin-resistant MRSA bloodstream isolates were analyzed. The minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) and levofloxacin (LEV) were determined before and after treatment with the efflux pump inhibitor CCCP. The isolates were classified as CCCP responsive or non-responsive based on a ≥4-fold reduction in CIP MICs. The associations of QRDR mutations in gyrA, gyrB, parC, and parE and virulence-associated genes with CCCP responsiveness were evaluated. Results: CCCP significantly reduced both CIP and LEV MICs, although changes in LEV MICs were limited to a subset of isolates. Of the 60 isolates, 15 were CCCP responsive, whereas 45 were non-responsive. The non-responsive isolates had significantly more QRDR mutations, particularly gyrA nucleotide mutations and GyrA amino acid substitutions. fnbA-positive isolates showed greater CCCP-mediated CIP MIC reductions and fewer QRDR nucleotide mutations, whereas seg-, sei-, and tst-positive isolates showed lower CCCP-mediated CIP MIC reductions and greater QRDR nucleotide mutation numbers. Conclusions: QRDR mutations and CCCP-responsive mechanisms were differentially associated with fluoroquinolone resistance phenotypes in MRSA. Their associations with distinct VF profiles suggest a potential relationship between CCCP responsiveness, QRDR mutation profiles, and the virulence genetic background of MRSA.
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BibTeX
@article{kim2026relative,
title = {{Relative Contributions of Quinolone Resistance-Determining Region Mutations and Efflux Pump-Associated Mechanisms to Fluoroquinolone Resistance in Staphylococcus aureus Clinical Isolates and Their Associations with Virulence Gene Profiles.}},
author = {Sohyeong Kim and Heechul Park and Minju Jung and Soyun Kim and Jieun Lim and Choseung Kim and Sangha Kim and Jinyoung Bae and Jiyoung Lee and Min Park and Sunghyun Kim},
journal = {Antibiotics (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/antibiotics15101006},
url = {https://europepmc.org/article/MED/42938747},
note = {CC BY},
}
RIS
TY - JOUR
TI - Relative Contributions of Quinolone Resistance-Determining Region Mutations and Efflux Pump-Associated Mechanisms to Fluoroquinolone Resistance in Staphylococcus aureus Clinical Isolates and Their Associations with Virulence Gene Profiles.
AU - Sohyeong Kim
AU - Heechul Park
AU - Minju Jung
AU - Soyun Kim
AU - Jieun Lim
AU - Choseung Kim
AU - Sangha Kim
AU - Jinyoung Bae
AU - Jiyoung Lee
AU - Min Park
AU - Sunghyun Kim
PY - 2026
DA - 2026/10/10
JO - Antibiotics (Basel, Switzerland)
DO - 10.3390/antibiotics15101006
UR - https://europepmc.org/article/MED/42938747
AB - Background: Fluoroquinolone resistance in methicillin-resistant Staphylococcus aureus (MRSA) involves multiple mechanisms, including quinolone resistance-determining region (QRDR) mutations and efflux pump activity. However, the relationship between these resistance mechanisms and virulence factors (VFs) remains unclear. This study investigated the relative contributions of QRDR mutations and carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-responsive mechanisms to fluoroquinolone resistance in MRSA and their associations with VF profiles. Methods: Sixty ciprofloxacin-resistant MRSA bloodstream isolates were analyzed. The minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) and levofloxacin (LEV) were determined before and after treatment with the efflux pump inhibitor CCCP. The isolates were classified as CCCP responsive or non-responsive based on a ≥4-fold reduction in CIP MICs. The associations of QRDR mutations in gyrA, gyrB, parC, and parE and virulence-associated genes with CCCP responsiveness were evaluated. Results: CCCP significantly reduced both CIP and LEV MICs, although changes in LEV MICs were limited to a subset of isolates. Of the 60 isolates, 15 were CCCP responsive, whereas 45 were non-responsive. The non-responsive isolates had significantly more QRDR mutations, particularly gyrA nucleotide mutations and GyrA amino acid substitutions. fnbA-positive isolates showed greater CCCP-mediated CIP MIC reductions and fewer QRDR nucleotide mutations, whereas seg-, sei-, and tst-positive isolates showed lower CCCP-mediated CIP MIC reductions and greater QRDR nucleotide mutation numbers. Conclusions: QRDR mutations and CCCP-responsive mechanisms were differentially associated with fluoroquinolone resistance phenotypes in MRSA. Their associations with distinct VF profiles suggest a potential relationship between CCCP responsiveness, QRDR mutation profiles, and the virulence genetic background of MRSA.
SN - 2079-6382
ER -