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

This study was designed to assess the influence of efflux pump activity on the biofilm formation in Typhimurium. subsp. serovar Typhimurium ATCC 19585 (ST ) and clinically isolated Typhimurium CCARM 8009 (ST ) 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 β-naphthylamide (PAβN) to compare efflux pump activity with biofilm-forming ability. The susceptibilities of ST and ST were increased in the presence of PAβN. ERY+PAβN showed the highest decrease in the minimum inhibitory concentration (MIC) of ERY from 256 to 2 μg/mL against ST and ST . The antimicrobial activity of NOR against planktonic cells was significantly increased in the presence of PAβN, showing the lowest numbers of ST (3.2 log CFU/cm ), and the TET+PAβN effectively inhibited the growth of ST (5.2 log CFU/cm ). The lowest biofilm-forming abilities were observed at NOR+PAβN against ST (biofilm-forming index, BFI < 0.41) and CEF+PAβN against ST (BFI = 0.32). The bacteria swimming motility and relative fitness varied depending on the antibiotic and PAβN treatments. The motility diameters of ST were significantly decreased by NOR+PAβN (6 mm) and TET+PAβN (15 mm), while the lowest motility of ST was observed at CIP+PAβN (8 mm). The significant decrease in the relative fitness levels of ST and ST was observed at CIP+PAβN and NOR+PAβN. The PAβN as an efflux pump inhibitor (EPI) can improve the antimicrobial and anti-biofilm efficacy of antibiotics against . 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.