Non-Invasive Model of Neuropathogenic &lt;em&gt;Escherichia coli&lt;/em&gt; Infection in the Neonatal Rat

Dalgakiran, Fatma; Witcomb, Luci A.; McCarthy, Alex J.; Birchenough, George; Taylor, Peter W.

doi:10.3791/52018-v

Cited by 1 publication

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Litter sizes ranged from 8–16 pups, with all pups in a single litter infected with the same strain. Infected newborn rats were monitored for 7 days employing an infection severity scoresheet as previously described 102 . Pups that displayed signs of suffering above the defined severity threshold were euthanised to minimise suffering.…”

Section: Methodsmentioning

confidence: 99%

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

Nhu,

Rahman,

Goh

et al. 2024

Nat Commun

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%