Mechanisms of mepA Overexpression and Membrane Potential Reduction Leading to Ciprofloxacin Heteroresistance in a Staphylococcus aureus Isolate
Abstract
1. Introduction
2. Results
2.1. The Ciprofloxacin Heteroresistance of Staphylococcus aureus 529
2.2. Genomic Characteristics Between 529 and 529_HR
2.3. Transcriptional Regulation of the Heteroresistant Subclone 529_HR
2.4. Limonene Changes the Heteroresistance Phenotype of 529
2.5. Reduced Membrane Potential Led to Heteroresistance
3. Discussion
4. Materials and Methods
4.1. Bacterial Strains
4.2. Antimicrobial Susceptibility Testing
4.3. Population Analysis Profiling
4.4. Stability Evaluations and Growth Curve
4.5. Whole-Genome Sequence and Sequence Analysis
4.6. RNA-seq and Transcriptomic Analysis
4.7. Determination of Limonene Inhibitory Effectiveness
4.8. DiOC2(3) Membrane Potential Measurement
4.9. RT-qPCR
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type | Gene | Substrate | |
---|---|---|---|
Resistance genes | Beta-lactams | blaZ | Methicillin |
Macrolides | erm(A) | Erythromycin | |
Aminoglycosides | spc | Spectinomycin | |
Rifamycins | rpoB | Rifampicin | |
Multidrug resistant efflux pumps | MFS family | norA, norB, norG | Ciprofloxacin |
sdrM | Norfloxacin Acriflavine Ethidium bromide | ||
MATE family | mepA | Ciprofloxacin Norfloxacin Tigecycline |
SNP Position | Gene | SNPs |
---|---|---|
188,068 | ggt | p.Val549Ser |
294,112 | essG_6 | p.Leu7Gln |
390,715 | ssl3 | p.Ile157Thr |
390,730 | p.ThrAspMetThr162LysGluIleAsn | |
798,468 | ssp | p.Gln200_Ser201dup |
1,043,951 | isdB | p.Glu71_Thr72delinsValAlaLysProValAla |
1,338,822 | asd | p.Asp242Glu |
1,378,171 | ebh | p.Asp8843Gly |
1,684,208 | lysP_2 | p.Glu375Gln |
1,684,220 | p.Lys371Glu | |
2,246,711 | farB_1 | p.Thr253Ser |
2,723,613 | clfB | p.Asp663Glu |
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Li, M.; Jian, Q.; Ye, X.; Jing, M.; Wu, J.; Wu, Z.; Ruan, Y.; Long, X.; Zhang, R.; Ren, H.; et al. Mechanisms of mepA Overexpression and Membrane Potential Reduction Leading to Ciprofloxacin Heteroresistance in a Staphylococcus aureus Isolate. Int. J. Mol. Sci. 2025, 26, 2372. https://doi.org/10.3390/ijms26052372
Li M, Jian Q, Ye X, Jing M, Wu J, Wu Z, Ruan Y, Long X, Zhang R, Ren H, et al. Mechanisms of mepA Overexpression and Membrane Potential Reduction Leading to Ciprofloxacin Heteroresistance in a Staphylococcus aureus Isolate. International Journal of Molecular Sciences. 2025; 26(5):2372. https://doi.org/10.3390/ijms26052372
Chicago/Turabian StyleLi, Mengyuan, Qianting Jian, Xinyi Ye, Mou Jing, Jia’en Wu, Zhihong Wu, Yali Ruan, Xiaoling Long, Rongmin Zhang, Hao Ren, and et al. 2025. "Mechanisms of mepA Overexpression and Membrane Potential Reduction Leading to Ciprofloxacin Heteroresistance in a Staphylococcus aureus Isolate" International Journal of Molecular Sciences 26, no. 5: 2372. https://doi.org/10.3390/ijms26052372
APA StyleLi, M., Jian, Q., Ye, X., Jing, M., Wu, J., Wu, Z., Ruan, Y., Long, X., Zhang, R., Ren, H., Sun, J., Liu, Y., Liao, X., & Lian, X. (2025). Mechanisms of mepA Overexpression and Membrane Potential Reduction Leading to Ciprofloxacin Heteroresistance in a Staphylococcus aureus Isolate. International Journal of Molecular Sciences, 26(5), 2372. https://doi.org/10.3390/ijms26052372