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

Nhu, Nguyen Thi Khanh, Rahman, M. Arifur, Goh, Kelvin G. K., Kim, Seung Jae, Phan, Minh-Duy, Peters, Kate M., Alvarez-Fraga, Laura, Hancock, Steven J., Ravi, Chitra, Kidd, Timothy J., Sullivan, Matthew J. ORCID: https://orcid.org/0000-0003-2276-3132, Irvine, Katharine M., Beatson, Scott A., Sweet, Matthew J., Irwin, Adam D., Vukovic, Jana, Ulett, Glen C., Hasnain, Sumaira Z. and Schembri, Mark A. (2024) A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria. Nature Communications, 15 (1). ISSN 2041-1723

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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.

Item Type: Article
Additional Information: Funding Information: We thank Thom Cuddihy, Rhys White and Barb Arnts for technical support. This work was supported by Australian National Health and Medical Research Council (NHMRC) Ideas grants 1181958 and 2001431 (to M.A.S., M.D.P. and N.T.K.N.), 2013776 (to J.V.), and 2021475 (to M.J.Su., K.G.K.G., and G.C.U.), as well as grants from the Gastroenterological Society of Australia (to S.Z.H.), the Australian Infectious Diseases Research Centre (to S.Z.H., and to M.A.S., A.D.I. and N.T.K.N.), The University of Queensland (to MAS and S.Z.H.), and the Mater Foundation (to S.Z.H.). J.V. is supported by a Senior Research Fellowship from the Sylvia and Charles Viertel Foundation. S.Z.H. was supported by an NHMRC Fellowship (2018–2022) and a University of Queensland Amplify Fellowship (2022–2024). M.J.Sw is supported by an NHMRC Investigator grant (APP1194406). Publisher Copyright: © The Author(s) 2024.
Uncontrolled Keywords: chemistry(all),biochemistry, genetics and molecular biology(all),physics and astronomy(all) ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 16 Apr 2024 13:30
Last Modified: 16 Apr 2024 13:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/94918
DOI: 10.1038/s41467-024-45176-4


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