Zabłotni Agnieszka, Schmidt Marek, Siwińska Małgorzata
Department of Biology of Bacteria, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland.
Int J Mol Sci. 2024 Dec 26;26(1):119. doi: 10.3390/ijms26010119.
The widespread and inappropriate use of antibiotics, for therapeutic and prophylactic purposes, has contributed to a global crisis of rapidly increasing antimicrobial resistance of microorganisms. This resistance is often associated with elevated mutagenesis induced by the presence of antibiotics. Additionally, subinhibitory concentrations of antibiotics can trigger stress responses in bacteria, further exacerbating this problem. In the present study, we investigated the effect of low doses of ciprofloxacin on the induction of the SOS response and the subsequent development of antibiotic resistance in spp. strains. Our findings revealed an increase in mutation frequencies within the studied strains, accompanied by a significant upregulation of expression. These observations were consistent across experiments involving two subinhibitory concentrations of ciprofloxacin. To establish mutation frequencies and assess gene expression changes, we utilized the Rif-to-Rif forward mutagenesis assay and RT-qPCR analysis, respectively. Furthermore, employing the microdilution method, we demonstrated that these changes could promote cross-resistance to multiple classes of antibiotics in spp. clinical strains. This, combined with the recurrent nature of -associated infections, poses a substantial risk of therapeutic failure. In conclusion, exposure to low doses of ciprofloxacin can significantly impact the susceptibility of bacilli, not only reducing their sensitivity to ciprofloxacin itself but also fostering resistance to other antibiotic classes. These findings underscore the importance of cautious antibiotic use and highlight the potential consequences of subinhibitory antibiotic exposure in clinical and environmental settings.
出于治疗和预防目的而广泛且不恰当地使用抗生素，已导致微生物抗微生物耐药性迅速增加这一全球危机。这种耐药性通常与抗生素的存在所诱导的诱变增加有关。此外，亚抑菌浓度的抗生素可引发细菌的应激反应，进一步加剧这一问题。在本研究中，我们调查了低剂量环丙沙星对 菌株中 SOS 反应的诱导以及随后抗生素耐药性发展的影响。我们的研究结果显示，在所研究的菌株中突变频率增加，同时 表达显著上调。在涉及两种亚抑菌浓度环丙沙星的实验中，这些观察结果都是一致的。为了确定突变频率并评估基因表达变化，我们分别使用了利福平到利福平正向诱变试验和 RT-qPCR 分析。此外，采用微量稀释法，我们证明这些变化可促进 临床菌株对多种类抗生素的交叉耐药性。这与 相关感染的复发性相结合，构成了治疗失败的重大风险。总之，暴露于低剂量环丙沙星可显著影响 杆菌的敏感性，不仅降低它们对环丙沙星本身的敏感性，还会增强对其他抗生素类别的耐药性。这些发现强调了谨慎使用抗生素的重要性，并突出了在临床和环境环境中亚抑菌抗生素暴露的潜在后果。
