TY - JOUR
T1 - Evolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,[5],12:i:- in Australia
AU - Ingle, Danielle J
AU - Ambrose, Rebecca L
AU - Baines, Sarah L
AU - Duchene, Sebastian
AU - Gonçalves da Silva, Anders
AU - Lee, Darren Y J
AU - Jones, Miriam
AU - Valcanis, Mary
AU - Taiaroa, George
AU - Ballard, Susan A
AU - Kirk, Martyn D
AU - Howden, Benjamin P
AU - Pearson, Jaclyn S
AU - Williamson, Deborah A
N1 - This work was supported by the National Health and Medical Research Council (NHMRC), Australia Project Grant (APP1129770). D.J.I. is supported by an NHMRC Investigator Grant (APP1195210). S.D. was funded by the ARC (DE190100805). M.D.K. is supported by an NHMRC Career Development Fellowship (APP1145997). B.P.H. is supported by an NHMRC Investigator Grant (APP1196103). J.S.P. is supported by an NHMRC Career Development Fellowship (APP1159230). D.A.W. is supported by an NHMRC Investigator Grant (APP1174555). The Microbiological Diagnostic Unit Public Health Laboratory is funded by the Department of Health and Human Services, Victoria.
PY - 2021/8/9
Y1 - 2021/8/9
N2 - Salmonella enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-) is a monophasic variant of Salmonella Typhimurium that has emerged as a global cause of multidrug resistant salmonellosis. We used Bayesian phylodynamics, genomic epidemiology, and phenotypic characterization to describe the emergence and evolution of Salmonella 4,[5],12:i:- in Australia. We show that the interruption of the genetic region surrounding the phase II flagellin, FljB, causing a monophasic phenotype, represents a stepwise evolutionary event through the accumulation of mobile resistance elements with minimal impairment to bacterial fitness. We identify three lineages with different population dynamics and discrete antimicrobial resistance profiles emerged, likely reflecting differential antimicrobial selection pressures. Two lineages are associated with travel to South-East Asia and the third lineage is endemic to Australia. Moreover antimicrobial-resistant Salmonella 4,[5],12:i- lineages efficiently infected and survived in host phagocytes and epithelial cells without eliciting significant cellular cytotoxicity, suggesting a suppression of host immune response that may facilitate the persistence of Salmonella 4,[5],12:i:-.
AB - Salmonella enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-) is a monophasic variant of Salmonella Typhimurium that has emerged as a global cause of multidrug resistant salmonellosis. We used Bayesian phylodynamics, genomic epidemiology, and phenotypic characterization to describe the emergence and evolution of Salmonella 4,[5],12:i:- in Australia. We show that the interruption of the genetic region surrounding the phase II flagellin, FljB, causing a monophasic phenotype, represents a stepwise evolutionary event through the accumulation of mobile resistance elements with minimal impairment to bacterial fitness. We identify three lineages with different population dynamics and discrete antimicrobial resistance profiles emerged, likely reflecting differential antimicrobial selection pressures. Two lineages are associated with travel to South-East Asia and the third lineage is endemic to Australia. Moreover antimicrobial-resistant Salmonella 4,[5],12:i- lineages efficiently infected and survived in host phagocytes and epithelial cells without eliciting significant cellular cytotoxicity, suggesting a suppression of host immune response that may facilitate the persistence of Salmonella 4,[5],12:i:-.
KW - Anti-Bacterial Agents/pharmacology
KW - Australia
KW - Bayes Theorem
KW - Cell Line
KW - Drug Resistance, Multiple, Bacterial/drug effects
KW - Evolution, Molecular
KW - Flagellin/genetics
KW - Humans
KW - Immunity
KW - Metals, Heavy/pharmacology
KW - Phylogeny
KW - Salmonella enterica/classification
KW - Salmonella typhimurium
KW - Serogroup
KW - THP-1 Cells
KW - Whole Genome Sequencing
U2 - 10.1038/s41467-021-25073-w
DO - 10.1038/s41467-021-25073-w
M3 - Article
C2 - 34373455
SN - 2041-1723
VL - 12
SP - 4786
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -