Ascites Bactericidal Capacity in Patients With Decompensated Cirrhosis

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Patients with decompensated cirrhosis face a high risk of bacterial infections, particularly spontaneous bacterial peritonitis (SBP).
• SBP is linked to gut bacterial translocation and immune dysfunction in cirrhosis.
• Common SBP pathogens may be gut pathobionts whose abundance increases with cirrhosis severity.

Purpose of the Study:

• To investigate the bactericidal capacity of cell-free ascites fluid (AF) and ascites macrophages in patients with decompensated cirrhosis.
• To characterize the virulence factors of common SBP pathogens and their interaction with the host immune system.

Main Methods:

• Assessed the killing of non-pathogenic *E. coli* K12 and pathogenic *E. coli* (ExPEC) and *Klebsiella pneumoniae* strains in cell-free AF.
• Utilized a genome-wide screen to identify bacterial genes essential for survival in AF.
• Evaluated the phagocytic and bactericidal activity of ascites macrophages against these bacteria.
• Infected mice with toxin-induced cirrhosis to assess bacterial burdens and clearance of wild-type and mutant strains.

Main Results:

• Pathogenic *E. coli* (ExPEC) and *Klebsiella pneumoniae* were resistant to killing in cell-free AF, unlike non-pathogenic *E. coli* K12.
• Genes involved in O-antigen biosynthesis, including the transcription factor RfaH, were critical for pathogen survival in AF.
• Ascites macrophages, particularly VSIG4^Hi cells, effectively phagocytosed and killed both pathogenic and non-pathogenic *E. coli*.
• Cirrhotic mice infected with ExPEC showed higher bacterial liver burdens, but rapidly cleared an *rfaH* mutant.

Conclusions:

• Bacterial capsule and O-antigen are key virulence factors enabling pathogens to evade host defenses in the cirrhotic ascites environment.
• Understanding bacterial virulence profiles, not just taxonomy, is vital for comprehending cirrhosis-associated dysbiosis.
• Targeting bacterial virulence factors or enhancing host macrophage function presents potential strategies to reduce SBP risk in cirrhosis.