A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria

Nguyen Thi Khanh Nhu, M. Arifur Rahman, Kelvin G. K. Goh, Seung Jae Kim, Minh-Duy Phan, Kate M. Peters, Laura Alvarez-Fraga, Steven J. Hancock, Chitra Ravi, Timothy J. Kidd, Matthew J. Sullivan, Katharine M. Irvine, Scott A. Beatson, Matthew J. Sweet, Adam D. Irwin, Jana Vukovic (), Glen C. Ulett (), Sumaira Z. Hasnain () and Mark A. Schembri ()
Additional contact information
Nguyen Thi Khanh Nhu: The University of Queensland
M. Arifur Rahman: The University of Queensland
Kelvin G. K. Goh: Griffith University
Seung Jae Kim: The University of Queensland
Minh-Duy Phan: The University of Queensland
Kate M. Peters: The University of Queensland
Laura Alvarez-Fraga: The University of Queensland
Steven J. Hancock: The University of Queensland
Chitra Ravi: The University of Queensland
Timothy J. Kidd: The University of Queensland
Matthew J. Sullivan: Griffith University
Katharine M. Irvine: The University of Queensland
Scott A. Beatson: The University of Queensland
Matthew J. Sweet: The University of Queensland
Adam D. Irwin: The University of Queensland
Jana Vukovic: The University of Queensland
Glen C. Ulett: Griffith University
Sumaira Z. Hasnain: The University of Queensland
Mark A. Schembri: The University of Queensland

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract 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 correlative association with many Enterobacteriaceae that cause severe human infection. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones.

Date: 2024
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DOI: 10.1038/s41467-024-45176-4

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