Diverse bacterial species contribute to antibiotic-associated diarrhoea and gastrointestinal damage - 12/07/18

Doi : 10.1016/j.jinf.2018.06.006

Sarah Larcombe ^a, Melanie L. Hutton ^a, Thomas V. Riley ^b, Helen E. Abud ^c, Dena Lyras ^a,^⁎
^a Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia
^b Department of Microbiology, PathWest Laboratory Medicine; School of Medical and Health Sciences, Edith Cowan University; School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia
^c Cancer Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia

^⁎Corresponding author.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Thursday 12 July 2018

Highlights

•	A diverse range of bacteria may cause antibiotic-associated diarrhoea (AAD).
•	Non-C. difficile AAD pathogens include antimicrobial resistant clinically important species.
•	Pathogens isolated show virulence potential based on encoded factors.
•	Isolates tested in vivo cause gut damage, targeting host processes essential for gut homeostasis.

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Summary

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.

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Keywords : Antibiotic-associated diarrhoea, Antimicrobial resistance, Bacterial pathogenesis, Clostridium difficile