Oral Presentation BACPATH 2022

Eating fats to stay alive: elucidating the mechanism of Salmonella enterica chronic infections. (#36)

Jessica L Rooke 1 , Rochelle Da Costa 1 , Jessica Gray 2 , Richard Strugnell 3 , Ian R Henderson 1
  1. Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia
  2. Institute for Microbiology and Infection, University of Birmingham, Birmingham, West Midlands, United Kingdom
  3. Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia

Salmonella enterica is a diverse pathogen that is well adapted to cause infections in various hosts. Up to 5% of S. enterica infections result in a phenomenon termed chronic carriage in both humans and animals. These chronic infections are often associated with gall bladder colonisation and enable bacteria to be shed through the infected hosts faeces and this facilitates the spread disease. In addition, these infections are often associated with biofilms on cholesterol gallstones and are resistant to routinely used antibiotics. While some known virulence proteins have been linked with gall bladder colonization and phospholipids identified as potential carbon sources in the host gall bladder, the mechanistic details connecting these two aspects remained unclear. We hypothesised that S. enterica effectors that contribute to chronic carriage would be highly conserved in S. enterica but not in other closely related Enterobacteriaceae. Using bioinformatics approaches, we identified 125 S. enterica specific genes that were absent in the genomes of Escherichia coli, Citrobacter rodentium, Yersinia pestis and Klebsiella pneumoniae. From this list of genes, we further characterised an outer membrane esterase. Loss of this esterase in Salmonella led to the inability to use lipids as a sole carbon source and decreased gall bladder colonization in murine models of infection. We demonstrate that this enzyme is essential for biofilm formation under lipid rich conditions and is a target for small molecule inhibitors. Our study provides evidence of a novel target to prevent, and or treat, chronic S. enterica infections.