Ascites Bactericidal Capacity in Patients With Decompensated Cirrhosis

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.

We investigated the bactericidal capacity of cell-free ascites fluid and ascites macrophages.

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 VSIG4^Hi 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.

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.