Programmed bacterial lysis in vivo alters host immune responses and microbial pathogenesis.

Controlled in vivo lysis of intestinal commensals by engineered Vibrio cholerae strains is linked to divergent mucosal immune responses that modulate bystander colonization and pathogenicity.

• Why it matters: It remains unclear how T6SS-driven bacterial antagonism increases mucosal host immune activation and thereby shapes disease severity, especially beyond the directly lysed cells.
• What they did: The authors engineered Vibrio cholerae lysis strains using CRISPR interference (CRISPRi) to knock down essential peptidoglycan biogenesis or lipopolysaccharide (LPS) transport genes, then analyzed lysis debris by mass spectrometry for proinflammatory muropeptides.
• The result: They found lysis debris muropeptides correlate with immune changes that directly modulate bystander V. cholerae colonization and pathogenicity, and oral co-administration of a synthetic peptidoglycan-derived metabolite with a V. cholerae ΔT6SS mutant—but not wild type—dramatically enhances disease symptoms.

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