Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2024

Cellulose disruption mutations drive enhanced bacterial virulence (#67)

Nhu TK Nguyen 1 2 , Arifur Rahman 3 , Kelvin GK Goh 4 , Seung Jae Kim 5 6 , Minh-Duy Phan 2 7 , Katharine M Irvine 2 3 , Matthew J Sweet 2 7 , Adam D Irwin 2 8 , Jana Vukovic 5 6 , Glen C Ulett 4 , Sumaira Z Hasnain 2 3 , Mark A Schembri 2 7
  1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
  2. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia
  3. Immunopathology Group, Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia
  4. School of Medical Sciences, and Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia
  5. School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia
  6. Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
  7. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
  8. University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Queensland

Bacteria adapt to selective pressure in their immediate environment in multiple ways. One mechanism involves the acquisition of independent mutations that disable or modify a key pathway, providing a signature of adaptation via convergent evolution. Extra-intestinal pathogenic Escherichia coli (ExPEC) belonging to sequence type 95 (ST95) represent a global clone frequently associated with severe human infections including acute pyelonephritis, sepsis, and neonatal meningitis. Here, we analysed a publicly available dataset of 613 ST95 genomes and identified a series of loss-of-function mutations that disrupt cellulose production or its modification in 55.3% of strains. We show the inability to produce cellulose significantly enhances ST95 invasive infection in a rat model of neonatal meningitis, leading to the disruption of intestinal barrier integrity in newborn pups and enhanced dissemination to the liver, spleen and brain. Consistent with these observations, disruption of cellulose production in ST95 augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of urinary tract infection. Mutations that disrupt cellulose production were also identified in other virulent ExPEC STs, Shigella and Salmonella, suggesting a wider impact of this pathoadaptive phenotype. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones.