한빛사논문
- 조회259
Nguyen Thi Khanh Nhu1,2,3,16, M. Arifur Rahman3,4,11,16, Kelvin G. K. Goh5,6,16, Seung Jae Kim7,8,16, Minh-Duy Phan1,2,3, Kate M. Peters1,2,3, Laura Alvarez-Fraga2,3,12, Steven J. Hancock2,3,13, Chitra Ravi1,2,3, Timothy J. Kidd2,3,14, Matthew J. Sullivan5,6,15, Katharine M. Irvine3,4, Scott A. Beatson2,3, Matthew J. Sweet1,3, Adam D. Irwin3,9,10, Jana Vukovic7,8, Glen C. Ulett5,6, Sumaira Z. Hasnain3,4 & Mark A. Schembri1,2,3
1Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.
2School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
3Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.
4Immunopathology Group, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Australia.
5School of Pharmacy and Medical Sciences, Griffith University, Southport, QLD, Australia.
6Menzies Health Institute Queensland, Griffith University, Southport, QLD, Australia.
7School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
8Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
9University of Queensland Centre for Clinical Research, Brisbane, Australia.
10Queensland Children’s Hospital, Brisbane, Australia.
11Present address: QIMR Berghofer Medical Research Institute, Brisbane QLD, Australia.
12Present address: INRAE, Univ Montpellier, LBE, 102 Avenue des Etangs, Narbonne 11100, France.
13Present address: Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK.
14Present address: Central Microbiology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia.
15Present address: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
16These authors contributed equally: Nguyen Thi Khanh Nhu, M. Arifur Rahman, Kelvin G. K. Goh, Seung Jae Kim.
Corresponding authors : Correspondence to Jana Vukovic, Glen C. Ulett, Sumaira Z. Hasnain or Mark A. Schembri.
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.
논문정보
- Research article
- 2024년 02월 (BRIC 등록일 2024-02-26)
- 국외 연구진
- 생명과학 > 생리학
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