Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2022

Understanding increased virulence of invasive multidrug resistant Salmonella enterica (82597)

Jaclyn S Pearson 1 2 , Rebecca L Ambrose 1 , Danielle J Ingle 3 4 , Deborah A Williamson 5 6
  1. Centre for Innate Immunity and Infectious Diseases, Hudson Institute Of Medical Research, Clayton, Victoria, Australia
  2. Department of Microbiology, Monash University, Melbourne, VIC, Australia
  3. Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia
  4. Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia
  5. Division of Infectious Diseases and Immune Defence, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
  6. Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia

Australia has one of the highest global rates of non-typhoidal salmonellosis. ST34 Salmonella 4,[5],12:i:- is a monophasic variant of non-typhoidal Salmonella (NTS) Typhimurium that has swept the globe in recent decades, becoming one of the leading causes of salmonellosis in humans today. In Australia, ST34 Salmonella 4,[5],12:i:- notifications now consistently outnumber those caused by other NTS. The key features of this emerging pathogen are 1) extensive multidrug resistance, 2) loss of the second flagella antigen FljB and 3) heavy metal resistance. Monophasic Salmonella are more likely to cause invasive disease in vulnerable populations, a feature reminiscent of typhoidal Salmonella serovars, and a dangerous prospect for public health. It is also concerning that there are no vaccines or therapeutics available to treat human salmonellosis, and as the prospect of limited-to-no antimicrobial therapeutic options for severe salmonellosis looms, it is critical that we understand the pathogenic mechanisms of ST34 Salmonella 4,[5],12:i:- and the specific host responses elicited during infection to inform future development of vaccines or host-directed therapies. Host detection of flagellin is a vital step in the induction of early inflammation and innate immune responses to intestinal pathogens, and thus the deletion of FljB in ST34 Salmonella 4,[5],12:i:- may indicate an evolutionary mechanism for Salmonella immune evasion and pathogenesis. However, to date, no studies have investigated the factors that influence intracellular replication and host responses to monophasic Salmonella. Our preliminary data shows that ST34 Salmonella 4,[5],12:i:- have unique infection outcomes compared to biphasic S. Typhimurium whereby they (i) replicate to high levels in macrophages without triggering additional cytotoxicity, and (ii) avoid activation of classic inflammatory and cell death pathways. Overall, our work supports the theory that the convergence of virulence and antimicrobial resistance is driving the emergence of this pandemic lineage globally.