RecA-mediated Adaptive Resistance Mechanism To Sub-inhibitory Concentration Tigecycline In Multidrug-resistance Acinetobacter Baumannii

Objective: Research the resistance of multiple-drug resistantAcinetobacter baumannii clinical isolates to tigecycline in North Sichuanarea; Whether sub-inhibitory concentration tigecycline can induceadaptive resistance and explain the MIC creep phenomenon; Whethersub-inhibitory concentration tigecycline can induce SOS response inAcinetobacter baumannii and the relationship between SOS response andefflux pump.Methods: Determine the multidrug-resistance Acinetobacterbaumannii MIC to tigecycline by broth microdilution method andresistant phenotype distribution by the standard of FDA; Inducemultidrug-resistance Acinetobacter baumannii by sub-inhibitoryconcentration tigecycline with/without thiourea, analysis MIC valueschanges after the induction and the adaptive resistance; Induced standardstrain by sub-inhibitory concentration tigecycline, determine the recA,SOS response related genes and adeB by qRT-PCR, analysis thecorrelation between RecA/SOS response and efflux pump activitychange.Results: The MICs of tigecycline against the50isolates ranged from 0.25～8μg/mL; MIC50is2μg/mL, while the MIC90is4μg/mL; With theMIC cut-offs set at2μg/ml and4μg/ml,56%and96%of theA.baumannii isolates, respectively, are susceptible. The interpretation ofMICs of tigecycline against A. baumannii isolates is according to theFDA susceptibility breakpoints,28isolates are susceptible,20isolates are intermediate, and2isolates are resistant; Susceptible rate,intermediate rate, and resistant rate are56.0%,40.0%, and4.0%,respectively. Sub-inhibitory concentration tigecycline can induce the MICcreep and thiourea can restrain this phenomenon. Sub-inhibitoryconcentration tigecycline can induce the upregulated expression of recAand adeB genes in A. baumannii ATCC19606, but not induce theupregulated expression of SOS response related genes.Conclusions：Tigecycline has good activity to multidrug-resistanceAcinetobacter baumannii (MIC502μg/ml、 MIC904μg/ml), but theresistance should not be ignored (resistance rate4%). Sub-inhibitoryconcentration tigecycline can induce the MIC creep inmultidrug-resistance Acinetobacter baumannii and the action is mediatedby RecA and effux pump. Sub-inhibitory concentration tigecycline caninduce the SOS response in ATCC19606. The relationship of RecA andefflux pump activity should be further researched.