Genomic epidemiology and phenotypic characterisation of Salmonella entericaserovar Panama in Victoria, Australia

Salmonella enterica serovar Panama, a causative agent of non-typhoidal salmonellosis (NTS), is one of several serovars that causes invasive NTS disease (iNTS) in humans. S. Panama is an understudied pathogen, with its pathobiology poorly understood. It is a predominant iNTS serovar in Australia, a high-income country with high rates of salmonellosis, where S. Panama has been documented to have a high odds ratio for causing iNTS. This study investigates the genomic epidemiology and antimicrobial resistance profiles of all S. Panama isolates recovered in Victoria, Australia, between 2000 and 2020. We examined the infection dynamics of S. Panama in seven isolates, representing the genetic diversity of the study population. Two sub-lineages, encompassed within a previously described Asian lineage, were identified. Multi-drug resistance (resistance to [≥]3 drug classes) was detected in 46 (51.7%) Australian isolates. The plasmid-mediated colistin resistance gene, mcr1.1, was detected in one Australian S. Panama isolate, carried by an IncI plasmid previously reported in Salmonella and Escherichia coli isolates collected from poultry in South-East Asia. Examination of the intracellular replication dynamics of S. Panama isolates demonstrated diverse phenotypes. In THP-1 derived macrophages, despite low host cell uptake, S. Panama showed higher replication rates over time compared to S. enterica serovar Typhimurium. However, a causative genotype could not be identified to explain this observed phenotype. This study provides insights into the S. Panama isolates imported into Australia over two-decades, showing MDR was common in this iNTS serovar, and colistin resistance reported for the first time. It provides the first data on the host-pathogen interactions of S. Panama in Australia, which will aid our collective understanding of the pathobiology of S. Panama and iNTS serovars more broadly. Author SummaryIn Australia, non-typhoidal Salmonella (NTS) cases have been on the rise since the 1970s; characterised by self-limiting enteritis, some NTS infections can result in systemic infections called invasive NTS disease. Salmonella enterica serovar Panama is a leading iNTS serovar in Australia. This study characterised the genomic epidemiology of S. Panama, identifying two lineages circulating in Australia over two decades and placing them within a global context. It also investigated the antimicrobial resistance (AMR) mechanisms of S. Panama, with multi-drug resistance commonly observed. Further, it identified the first plasmid-mediated colistin-resistant S. Panama in Australia. We additionally examined the characteristics of S. Panama-mediated host-pathogen interactions in both epithelial and macrophage cells lines, providing the first insight into the infection dynamics of this understudied pathogen. Thus, this study combines genomics and in vitro infection experiments to understand the pathogenic behaviour of the neglected iNTS S. Panama.