Generation and microevolution of Salmonella 4,[5],12:i:- from Salmonella enterica serovar Typhimurium by complicated transpositions

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. Replacement of the fljAB operon in S. Typhimurium by different resistance regions (RRs) can generate Salmonella 4,[5],12:i:- without expressing the second-phase flagellar antigen. However, the generation and evolution of RRs in Salmonella 4,[5],12:i:- across the world remain unknown. In the present study, except for the three reported RRs (RR1–RR3), five novel RRs (RR4–RR8) were identified in Chinese isolates from livestock and humans. The insertion of RR3 into the chromosomal hin - iroB site of S. Typhimurium produced RR3- S. Typhimurium as a primary intermediate strain. Following cis and/or trans intramolecular transpositions mediated by IS 26 and/or IS 1R elements, Salmonella 4,[5],12:i:- was produced by replacing the fljAB operon and/or its flanking sequences with RRs; the generation process was confirmed by the subcultivation of RR3- S. Typhimurium in vitro and in vivo . In addition, animal experiments revealed that RR3- Salmonella 4,[5],12:i:- displayed more efficient colonisation and survival abilities in mouse tissues than its parent strain, RR3- S. Typhimurium. The present study is the first to demonstrate the molecular mechanism underlying the origin and generation of Salmonella 4,[5],12:i:- from S. Typhimurium through complicated transpositions.