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Phenotypic Changes Associated With Evolution of Colistin Resistance in ST11 Carbapenem-Resistant

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Abstract

Colistin is one of the few antibiotics that exhibit bactericidal effect on carbapenemase-producing strains. In recent years, however, colistin resistance is increasingly being reported among clinical carbapenem-resistant strains worldwide, posing serious challenge to treatment of infections caused by these organisms. In this study, we investigated one colistin-susceptible (YJH4) and one colistin-resistant (YJH15) strain, which were collected from a patient before and after colistin treatment, respectively. We characterized the effects of inactivation-induced colistin resistance on the physiological fitness and virulence in ST11 carbapenem-resistant both and . The colistin-resistant strain YJH15 was found to exhibit increased fitness and biofilm formation potential , and increased survival rate in the presence of normal human serum. Interestingly, YJH15 exhibited reduced virulence in the mouse infection model but enhanced virulence in infection model when compared to the colistin-susceptible parental strain YJH4. Infection with YJH15 was also found to result in lower expression level of inflammatory cytokine IL-1β in blood and significantly decreased bacterial loads in heart, liver, spleen, lung, kidney and blood. These results demonstrated that inactivation-induced colistin resistance has significant effects on multiple fitness and virulence-associated traits in .

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