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2026

Cell Mol Gastroenterol Hepatol. 2026 May 21;20(9):101812. doi: 10.1016/j.jcmgh.2026.101812. Online ahead of print.

Ascites Bactericidal Capacity in Patients With Decompensated Cirrhosis

Isanka U Ratnasekera, Min-Duy Phan, Nhu Nguyen, Eline E Jessen, Sahar Keshvari, Yvette Ong, Timothy J Kidd, Steven J Hancock, Samuel A S Morris, David P Sester, David A Hume, Elizabeth E Powell, Matthew J Sweet, Mark A Schembri, Katharine M Irvine

Mater Research - The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia. Institute for Molecular Bioscience (IMB), The University of Queensland, St Lucia, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland, Australia. Institute for Molecular Bioscience (IMB), The University of Queensland, St Lucia, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia. Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia. Novoviah, Brisbane, Queensland, Australia. Centre for Liver Disease Research, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia; QIMR-Berghofer Medical Research Institute, Herston, Queensland, Australia. Institute for Molecular Bioscience (IMB), The University of Queensland, St Lucia, Queensland, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia. Mater Research - The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia; Centre for Liver Disease Research, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia.

Service type: Stock strains

Abstract

Background & aims: Patients with decompensated cirrhosis are at high risk of developing bacterial infections. The most common infection is spontaneous bacterial peritonitis in ascites fluid, caused by gut bacterial translocation and facilitated by cirrhosis associated immune dysfunction. Common causative agents of spontaneous bacterial peritonitis are thought to represent pathobionts that increase in abundance in the gut with cirrhosis severity, rather than opportunistic commensals. Despite this there have been few studies describing the characteristics of spontaneous bacterial peritonitis pathogens and immune responses to them. Methods: We investigated the bactericidal capacity of cell-free ascites fluid and ascites macrophages. Results: Nonpathogenic Escherichia coli K12 was rapidly killed in cell-free ascites fluid, whereas extraintestinal pathogenic E coli and Klebsiella pneumoniae strains, representative of the most common causes of spontaneous bacterial peritonitis, were resistant. A transposon-based genome-wide screen identified a requirement for genes involved in O-antigen biosynthesis for survival of both organisms in cell-free ascites fluid, including the transcription factor RfaH, which controls expression of surface polysaccharides. Although extraintestinal pathogenic E coli were resistant to fluid-mediated killing, ascites macrophages, especially VSIG4Hi cells, phagocytosed and killed extraintestinal pathogenic E coli and nonpathogenic E coli K-12 with similar efficacy. Mice with toxin-induced cirrhosis had higher bacterial burdens in the liver compared with control mice when infected with extraintestinal pathogenic E coli, but rapidly cleared an rfaH mutant attenuated for capsule and O-antigen biosynthesis. Conclusions: These data highlight the importance of understanding bacterial virulence profiles in addition to taxonomy in cirrhosis dysbiosis and identify critical roles for capsule and O-antigen in host evasion by spontaneous bacterial peritonitis-associated pathogens. Targeting bacterial virulence factors and/or host macrophage functions may reduce the risk of spontaneous bacterial peritonitis in cirrhosis.