A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Journal Articles Nature Communications Year : 2024

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

Kelvin G K Goh
Seung Jae Kim
Minh-Duy Phan
Katharine M Irvine
Scott A Beatson
Glen C Ulett
Sumaira Z Hasnain

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. Extra-intestinal pathogenic Escherichia coli cause urinary tract and bloodstream infections. Here, the authors show how mutations that disrupt the production of cellulose, a polysaccharide produced by many bacteria, drive enhanced virulence.
Fichier principal
Vignette du fichier
Thi-Khanh-Nhu-NC-2024-CC-BY.pdf (4.91 Mo) Télécharger le fichier
Origin Publisher files allowed on an open archive
Licence

Dates and versions

hal-04664754 , version 1 (30-07-2024)

Licence

Identifiers

Cite

Nguyen Thi Khanh Nhu, M Arifur Rahman, Kelvin G K Goh, Seung Jae Kim, Minh-Duy Phan, et al.. A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria. Nature Communications, 2024, 15, ⟨10.1038/s41467-024-45176-4⟩. ⟨hal-04664754⟩
197 View
2 Download

Altmetric

Share

More