Evolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,[5],12:i:- in Australia

• Published in: Nature communications Vol. 12; no. 1; pp. 4786 - 13
• Main Authors: Ingle, Danielle J., Ambrose, Rebecca L., Baines, Sarah L., Duchene, Sebastian, Gonçalves da Silva, Anders, Lee, Darren Y. J., Jones, Miriam, Valcanis, Mary, Taiaroa, George, Ballard, Susan A., Kirk, Martyn D., Howden, Benjamin P., Pearson, Jaclyn S., Williamson, Deborah A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 631/181/757; 631/326/1320; 631/326/325/2482; Anti-Bacterial Agents - pharmacology; Antimicrobial agents; Antimicrobial resistance; Australia; Bayes Theorem; Bayesian analysis; Cell Line; Cytotoxicity; Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - genetics; Epidemiology; Epithelial cells; Epithelium; Evolution; Evolution, Molecular; Flagellin; Flagellin - genetics; Humanities and Social Sciences; Humans; Immune response; Immunity; Metals, Heavy - pharmacology; multidisciplinary; Multidrug resistance; Multidrug resistant organisms; Phagocytes; Phenotypes; Phylogeny; Population dynamics; Salmonella; Salmonella enterica; Salmonella enterica - classification; Salmonella enterica - drug effects; Salmonella enterica - genetics; Salmonella typhimurium; Salmonellosis; Science; Science (multidisciplinary); Serogroup; THP-1 Cells; Toxicity; Whole Genome Sequencing; Australia
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25073-w

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:-. Salmonella enterica serovar 4,[5],12:i:- ( Salmonella 4,[5],12:i:-) is a major pathogen of humans and animals with a reported incidence in Australia three times higher than the UK and USA. Here, the authors report the circulation, antimicrobial resistance signatures, and effects on host cells, of three Salmonella 4,[5],12:i:- lineages within Australia.