title: Assessment of altered binding specificity of bacteriophage for ciprofloxacin-induced antibiotic-resistant Salmonella Typhimurium.
abstract: This study describes a new effort toward understanding the interaction mechanisms between antibiotic-resistant Salmonella Typhimurium and phages. The antibiotic susceptibility, β-lactamase activity, bacterial motility, gene expression, and lytic activity were evaluated in ciprofloxacin-induced antibiotic-sensitive Salmonella Typhimurium (ASST(CIP)) and ciprofloxacin-induced antibiotic-resistant S. Typhimurium (ARST(CIP)), which were compared to the wild-type strains (ASST(WT) and ARST(WT)). The MIC values of ampicillin, norfloxacin, chloramphenicol, and tetracycline were significantly increased to > 512, 16, 16, and 256 μg/ml, respectively, in the ARST(CIP). The lowest and highest extracellular lactamase activities were observed in ASST(WT) (6.85 μmol/min/ml) and ARST(CIP) (48.83 μmol/min/ml), respectively. The acrA, lpfE, and hilA genes were significantly upregulated by more than tenfold in both ASST(CIP) and ARST(CIP). The induction of multiple antibiotic resistance resulted from the increased efflux pump activity (AcrAB-TolC). The highest phage adsorption rates were more than 95 % for ASST(WT), ASST(CIP), and ARST(WT), while the lowest adsorption rate was 52 % for ARST(CIP) at 15 min of infection. The least lytic activity of phage was 20 % against the ARST(CIP), followed by ASST(CIP) (30 %). The adsorption rate of phage against ARST(CIP) was 52 % at 15 min of infection, which resulted in the decrease in lytic activity (12 %). Understanding the interaction of phage and bacteria is essential for the practical application of phage to control and detect antibiotic-resistant bacteria. The results provide useful information for understanding the binding specificity of phages for multiple antibiotic-resistant pathogens.
authors.affiliation: Department of Medical Biomaterials Engineering and Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
authors.forename: Jeongjin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Medical Biomaterials Engineering and Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Jo
authors.affiliation: Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Ding
authors.affiliation: School of Convergence Bioscience and Technology, Seowon University, Cheongju, Chungbuk, 28674, Republic of Korea.
authors.forename: Hyeon-Yong
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Medical Biomaterials Engineering and Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea. juheeahn@kangwon.ac.kr.
authors.forename: Juhee
authors.initials: J
authors.lastname: Ahn
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D001435:Bacteriophages / Q000235:genetics*; D001665:Binding Sites; D002701:Chloramphenicol / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics* / Q000821:virology; D013752:Tetracycline / Q000494:pharmacology; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C102236:HilA protein, Salmonella; D026901:Membrane Transport Proteins; D015534:Trans-Activators; D002939:Ciprofloxacin; D002701:Chloramphenicol; D000667:Ampicillin; D001618:beta-Lactamases; D013752:Tetracycline; D009643:Norfloxacin
keywords: Antibiotic resistance; Bacteriophage; Ciprofloxacin; Efflux pump; Lactamase; Lytic activity; Salmonella