Active efflux pump adeB is involved in multidrug resistance of Acinetobacter baumannii induced by antibacterial agents

Abstract

Abstract. The aim of the present study was to investigate the resistance of Acinetobacter baumannii, which was induced by cefepime (FEP), cefoperazone-sulbactam (SCF), tazobactam (TZP), levofloxacin (LEV), amikacin (AK), imipenem (IPM), and ciprofloxacin (CIP), in vitro. Multi-step drug resistance selection of 16 A. baumannii strains was performed using seven antibacterial agents (FEP, TZP, CIP, AK, IPM, SCF, and LEV). The minimum inhibitory concentration (MIC) was determined using the agar dilution method. Random amplified polymorphic DNA polymerase chain reaction was performed to analyze the genotypes and the carrying rates of aac (3) (8-to 128-fold) were noted in the MIC and different genotypes were showed in RAPD of the strains before and after performing the drug resistant test. PCR data revealed significant differences (P<0.05) between the carrying rates of resistant genes before and after drug induction, with the exception of rmtA, OXA-24, TEM-1, and IMP. Significant increases were demonstrated in the comparative adeB grayscale in strains that underwent drug induction when compared with the sensitive strains (55.69±43.11% vs. 10.08±26.35%; P=0.001). Findings of the present study suggest that the active efflux pump, adeB, has an important role in multidrug resistance of the A. baumannii induced by antibacterial agents in vitro. IntroductionAlthough carbapenems antibiotics remain the backbone therapy for severe suspected bacterial infections, resistance to this antimicrobial treatment has been increasingly reported (1). Thus, therapeutic options have become limited. Multidrug-resistance to antibiotics currently available, in particular in Gram-negative bacteria, has created a critical global medical challenge (2). Acinetobacter baumannii is frequently observed as a nosocomial infection, which causes high mortality, morbidity and hospitalization cost (3). Crude mortality rate and attributable mortality of the infection were reported to be 52 and 10-35%, respectively (4). Multidrug-resistant A. baumannii is considered as a leading cause of nosocomial infection, particularly in critically ill patients (5). A. baumannii has been reported to be resistant to a broad range of antimicrobial agents, and the tendency for its epidemic spread has subsequently extended (6). An increasing drug resistance of A. baumannii to carbapenems has been demonstrated by the SENTRY Antimicrobial Surveillance Program, whose objective was to report antimicrobial susceptibility and pathogen occurrence data for >40,000 episodes of BSI in 72 medical centers representing 22 nations since January 1997 (7). The emergence of multidrug and pandrug-resistant A. baumannii has caused major threats to the infection control and treatment plans in clinical practices (8). According to our knowledge, drug resistance of A. baumannii is closely related with the application of antibacterial agents. However, few studies have been performed to investigate whether a single antibacterial agent was able to induce pandrug resistance of A. baumannii. In the...

Integrative analysis of outer membrane vesicles proteomics and whole-cell transcriptome analysis of eravacycline induced Acinetobacter baumannii strains

“…baumannii [27]. The role of similar overexpression of adeB has been noted in some MDR isolates resistant to tigecycline in some of the previous research works [28].…”

Integrative analysis of outer membrane vesicles proteomics and whole-cell transcriptome analysis of eravacycline induced Acinetobacter baumannii strains

“…baumannii [23]. The role of similar overexpression of adeB has been noted in some MDR isolates resistant to tigecycline in some of the previous research works [24].…”

Integrative analysis of outer membrane vesicles proteomics and whole-cell transcriptome analysis of eravacycline induced Acinetobacter baumannii strains

“…Eravacycline resistance in A. baumannii due to AdeABC efflux has not been reported before; hence, this upregulation can be attributed to the induction due to the antibiotic even though it is not a substrate for the pump. Antibiotic induced adeB efflux pump resistance has a major influence on the resistance status of A. baumannii [26]. The role of similar overexpression of adeB has been noted in some MDR isolates resistant to tigecycline in some of the previous research works [27].…”