Increased Expression of AbcA Efflux Pump Accelerated Resistance Development from Tolerance to Resistance Against Oxacillin in .

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.