Role of Efflux Pump-Mediated Antibiotic Resistance in Quorum Sensing-Regulated Biofilm Formation by Salmonella Typhimurium

초록

This study was designed to assess the influence of efflux pump activity on the biofilm formation in Salmonella Typhimurium. Salmonella enterica subsp. enterica serovar Typhimurium ATCC 19585 (STWT) and clinically isolated S. Typhimurium CCARM 8009 (STCI) were treated with ceftriaxone (CEF), chloramphenicol (CHL), ciprofloxacin (CIP), erythromycin (ERY), norfloxacin (NOR), and tetracycline (TET) in autoinducer-containing media in the absence and presence of phenylalanine-arginine beta-naphthylamide (PA beta N) to compare efflux pump activity with biofilm-forming ability. The susceptibilities of STWT and STCI were increased in the presence of PA beta N. ERY+PA beta N showed the highest decrease in the minimum inhibitory concentration (MIC) of ERY from 256 to 2 mu g/mL against STWT and STCI. The antimicrobial activity of NOR against planktonic cells was significantly increased in the presence of PA beta N, showing the lowest numbers of STWT (3.2 log CFU/cm(2)), and the TET+PA beta N effectively inhibited the growth of STCI (5.2 log CFU/cm(2)). The lowest biofilm-forming abilities were observed at NOR+PA beta N against STWT (biofilm-forming index, BFI < 0.41) and CEF+PA beta N against STCI (BFI = 0.32). The bacteria swimming motility and relative fitness varied depending on the antibiotic and PA beta N treatments. The motility diameters of STWT were significantly decreased by NOR+PA beta N (6 mm) and TET+PA beta N (15 mm), while the lowest motility of STCI was observed at CIP+PA beta N (8 mm). The significant decrease in the relative fitness levels of STWT and STCI was observed at CIP+PA beta N and NOR+PA beta N. The PA beta N as an efflux pump inhibitor (EPI) can improve the antimicrobial and anti-biofilm efficacy of antibiotics against S. Typhimurium. This study provides useful information for understanding the role of efflux pump activity in quorum sensing-regulated biofilm formation and also emphasizes the necessity of the discovery of novel EPIs for controlling biofilm formation by antibiotic-resistant pathogens.

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