Emerging high-level ciprofloxacin resistance and molecular basis of resistance in Salmonella enterica from humans, food and animals

Disease caused by nontyphoidal serotypes of Salmonella enterica is the leading cause of foodborne illness worldwide. Many serotypes have also developed resistance to antimicrobials commonly used for the treatment of salmonellosis. Here we analyze 179 ciprofloxacin-resistant isolates identified among 3680 Salmonella isolated from humans, food, animals, and water collected in Shanghai, China. They were assessed for antimicrobial susceptibility, plasmid-mediated quinolone resistance (PMQR) determinants, and mutations in quinolone resistance determination regions (QRDRs); genetic relatedness was examined using PFGE. Ciprofloxacin resistance in Salmonella increased from 2.3% in 2006 to 5.9% in 2012. Multidrug resistance was common, and most carried mutations in QRDR (97.2%) and PMQR determinants (71.5%). Mutations frequently included changes in gyrA: Ser83Phe (53.6%) and Asp87Asn (35.8%), and in parC: Thr57Ser (53.1%) and Ser80Arg (44.1%). Mutations in parC and parE without changes in gyrA were identified in S. Derby and most S. Thompson. Among PMQR determinants, aac(6')-Ib-cr (62.0%) and oqxA/oqxB (33.5%/33.0%) were most common, and conferred resistance without target mutations in five S. Typhimurium isolates. PFGE analysis revealed that S. Typhimurium, isolated from pork and aquatic products, and S. Indiana, isolated from chicken, were highly similar to isolates from humans, suggesting these products be the major source of ciprofloxacin-resistant infections. Our findings highlight the important role QRDRs and PMQR play in ciprofloxacin resistance of Salmonella, and reveal the potential sources of the pathogen associated with human infections.