Diverse bacterial species contribute to antibiotic-associated diarrhoea and gastrointestinal damage

Document Type

Journal Article

Publication Title

The Journal of Infection

ISSN

1532-2742

Volume

77

Issue

5

First Page

417

Last Page

426

PubMed ID

29964142

Publisher

Elsevier

School

School of Medical and Health Sciences

RAS ID

27337

Comments

Larcombe, S., Hutton, M. L., Riley, T. V., Abud, H. E., & Lyras, D. (2018). Diverse bacterial species contribute to antibiotic-associated diarrhoea and gastrointestinal damage. Journal of Infection, 77(5), 417-426. Available here

Abstract

OBJECTIVES: Antibiotic-associated diarrhoea (AAD) caused by C. difficile is one of the most common nosocomial infections, however, little is known about infections related to antimicrobial use for pathogens other than C. difficile. We therefore aimed to provide insight into other bacterial causes of AAD, and how infection with these pathogens causes damage in the dysbiotic gut.

METHODS: Clinical isolates from C. difficile-negative AAD patients were whole genome sequenced for in silico analysis of potential virulence factors and antimicrobial resistance determinants. A mouse model of infection was developed to assess the capacity of these isolates to cause gastrointestinal damage, which was analysed by studying specific markers in the gastrointestinal mucosa of infected mice.

RESULTS: Several bacterial pathogens were isolated from patients with C. difficile-negative AAD. Each isolate showed the potential for virulence based on encoded virulence factors, as well as most showing antimicrobial resistance in vitro. Isolates of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were tested in the mouse model of infection, inducing damage primarily in the small intestine, affecting adherens junction integrity, cellular polarity, and cellular proliferation.

CONCLUSIONS: Several pathogens of clinical importance other than C. difficile are able to cause gastrointestinal infection following antimicrobial-mediated dysbiosis. The virulence potential and multidrug resistance identified in these isolates illuminates the importance of further diagnostic screening in cases of C. difficile-negative AAD.

DOI

10.1016/j.jinf.2018.06.006

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