Yu Xiaohui, Liu Miaomiao, Liu Pilong, Hao Zehua, Zhao Lili, Zhao Xin
Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang 050017, China.
College of Animal Science and Technology, Northwest A&F University, Xianyang 712100, China.
Microorganisms. 2025 May 16;13(5):1140. doi: 10.3390/microorganisms13051140.
Bacterial tolerance, especially in (), may arise under intermittent antibiotic regimens and act as a stepping stone toward resistance development. However, the transition from tolerance to resistance and its contributing factors remain poorly understood. This study explores the role of the efflux pump gene in this process. mutants (overexpression, knockout, and complementation) were constructed via homologous recombination. These strains were subjected to 21 cycles of intermittent exposure to oxacillin at 20× MIC, and the resistance evolution was monitored. Spontaneous mutation frequencies and survival abilities in these mutants were also measured to determine their involvement in resistance development. The overexpression mutant exhibited a faster development of resistance compared to the wildtype strain. Conversely, the knockout mutant maintained susceptibility to oxacillin, with no significant changes in the relative MIC. Increased mutation frequency and enhanced survival were observed in the overexpression strain, whereas both were reduced in the knockout. overexpression significantly accelerated the development of oxacillin resistance in by promoting spontaneous mutations and bacterial survival. Disrupting may offer a novel strategy to prevent the evolution of antibiotic resistance.
细菌耐受性，尤其是在（）中，可能在间歇性抗生素治疗方案下产生，并成为耐药性发展的垫脚石。然而，从耐受性到耐药性的转变及其促成因素仍知之甚少。本研究探讨了外排泵基因在这一过程中的作用。通过同源重组构建了（外排泵基因）突变体（过表达、敲除和互补）。这些菌株在20倍最低抑菌浓度（MIC）下接受21个周期的间歇性苯唑西林暴露，并监测耐药性演变。还测量了这些突变体的自发突变频率和生存能力，以确定它们在耐药性发展中的作用。与野生型菌株相比，外排泵基因过表达突变体表现出更快的耐药性发展。相反，外排泵基因敲除突变体对苯唑西林保持敏感，相对MIC无显著变化。在过表达菌株中观察到突变频率增加和生存能力增强，而在敲除菌株中两者均降低。外排泵基因过表达通过促进自发突变和细菌存活，显著加速了（细菌）对苯唑西林耐药性的发展。破坏（外排泵基因）可能为预防抗生素耐药性的演变提供一种新策略。
