Microevolution of Salmonella 4,[5],12:i:- derived from Salmonella enterica serovar Typhimurium through complicated transpositions
Zhenyu Wang,
Dan Gu,
Yaming Hong,
Yachen Hu,
Jiaojie Gu,
Yuanyue Tang,
Xiaohui Zhou,
Yunzeng Zhang,
Xinan Jiao,
Qiuchun Li
Affiliations
Zhenyu Wang
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China
Dan Gu
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China
Yaming Hong
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China
Yachen Hu
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China
Jiaojie Gu
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China
Yuanyue Tang
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China
Xiaohui Zhou
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA; School of Public Health and Emergency Management, Southern University of Science and Technology, 1088 Xueyuan Road, Nanshan District, Shenzhen 518055, Guangdong, China
Yunzeng Zhang
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Corresponding author
Xinan Jiao
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Corresponding author
Qiuchun Li
Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Jiangsu Key Lab of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-product Safety, Yangzhou University, 48 Wenhui East Road, Yangzhou 225000, Jiangsu, China; Corresponding author
Summary: Salmonella enterica subsp. enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-), derived from S. Typhimurium, has become the dominant serotype causing human salmonellosis. In this study, we define the genetic mechanism of the generation of Salmonella 4,[5],12:i:- from S. Typhimurium through complicated transpositions and demonstrate that Salmonella 4,[5],12:i:- displays more efficient colonization and survival abilities in mice than its parent S. Typhimurium strain. We identified intermediate strains carrying both resistance regions (RRs) and the fljAB operon for the generation of Salmonella 4,[5],12:i:-. The insertion of RR3 into the chromosomal hin-iroB site of S. Typhimurium produced RR3-S. Typhimurium as a primary intermediate. Salmonella 4,[5],12:i:- was then produced by replacing the fljAB operon and/or its flanking sequences through intramolecular transpositions mediated by IS26 and/or IS1R elements in RR3-S. Typhimurium, which was further confirmed both in vitro and in vivo. Overall, we demonstrate the molecular mechanism underlying the origin, generation, and advantage of RRs-Salmonella 4,[5],12:i:- from S. Typhimurium.
