Emerging Aeromonas enteric infections: their association with inflammatory bowel disease and novel pathogenic mechanisms

Seul A Lee; Fang Liu; Christopher Yuwono; Monique Phan; Sarah Chong; Joanna Biazik; Alfred Chin Yen Tay; Michael Janitz; Stephen M Riordan; Ruiting Lan; Michael C Wehrhahn; Li Zhang

doi:10.1128/spectrum.01088-23

Emerging Aeromonas enteric infections: their association with inflammatory bowel disease and novel pathogenic mechanisms

Microbiol Spectr. 2023 Sep 21;11(5):e0108823. doi: 10.1128/spectrum.01088-23. Online ahead of print.

Authors

Affiliations

¹ School of Biotechnology and Biomolecular Sciences, University of New South Wales , Sydney, New South Wales, Australia.
² Mark Wainwright Analytical Centre, University of New South Wales , Sydney, New South Wales, Australia.
³ Helicobacter Research Laboratory, School of Pathology and Laboratory Medicine, Marshall Centre for Infectious Diseases Research and Training, University of Western Australia , Perth, Australia.
⁴ Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales , Sydney, New South Wales, Australia.
⁵ Douglass Hanly Moir Pathology, a Sonic Healthcare Australia Pathology Practice , Macquarie Park, New South Wales, Australia.

^# Contributed equally.

Abstract

Aeromonas species are emerging human enteric pathogens. This study examines the isolation of Aeromonas and other enteric bacterial pathogens from patients with and without inflammatory bowel disease (IBD). This study also investigates the intestinal epithelial pathogenic mechanisms of Aeromonas veronii. The isolation rates of seven enteric bacterial pathogens from 2,279 patients with IBD and 373,276 non-IBD patients were compared. An A. veronii strain (AS1) isolated from intestinal biopsies of a patient with IBD was used for pathogenic mechanism investigation, and Escherichia coli K12 was used as a bacterial control. HT-29 cells were used as a model of human intestinal epithelium. A significantly higher isolation of Aeromonas species was found in patients with IBD as compared to non-IBD patients (P = 0.0001, odds ratio = 2.11). A. veronii upregulated 177 inflammatory genes and downregulated 52 protein-coding genes affecting chromatin assembly, multiple small nuclear RNAs, multiple nucleolar RNAs, and 55 cytoplasmic tRNAs in HT-29 cells. These downregulation effects were unique to A. veronii and not observed in HT-29 cells infected with E. coli K12. A. veronii induced intestinal epithelial apoptosis involving the intrinsic pathway. A. veronii caused epithelial microvilli shortening and damage and epithelial production of IL-8. In conclusion, this study for the first time reports the association between IBD and Aeromonas enteric infection detected by bacterial cultivation. This study also reports that A. veronii damages intestinal epithelial cells via multiple mechanisms, of which the downregulating cytoplasmic tRNA, small nuclear RNA, and small nucleolar RNA are novel bacterial pathogenic mechanisms. IMPORTANCE This study for the first time reports the association between inflammatory bowel disease (IBD) and Aeromonas enteric infection detected by bacterial pathogen cultivation, highlighting the need of clinical and public health attention. The finding that patients with IBD are more susceptible to Aeromonas enteric infection suggests that detection of Aeromonas enteric infection should be routinely performed for the diagnosis and treatment of IBD. This study also reports novel bacterial pathogenic mechanisms employed by Aeromonas veronii. Through comparative transcriptomic analysis and other techniques, this study revealed the pathogenic mechanisms by which A. veronii causes damage to intestinal epithelial cells. Among the various pathogenic mechanisms identified, the downregulating tRNA, small nuclear and nucleolar RNAs in human intestinal epithelial cells are novel bacterial pathogenic mechanisms.

Keywords: Aeromonas; Aeromonas caviae; Aeromonas veronii; Campylobacter; IBD; Salmonella; Shigella; enteric infection; intestinal epithelial cells; transcriptome.