Engineered probiotics target granulomas to treat mycobacterial infection

Engineered probiotic Escherichia coli Nissle 1917 infiltrates and colonizes mycobacterial granulomas and, when programmed, suppresses drug-sensitive and drug-resistant mycobacteria.

• Why it matters: Granulomas are a difficult-to-reach niche where mycobacteria persist, limiting how well conventional drugs can access and eliminate infection.
• What they did: The team used granuloma hypoxia to restrict bacterial growth and built a dual-mode lysis circuit for sustained payload release, plus a mycobacteriophage-derived enzyme to target mycobacteria.
• The result: Engineered probiotics reduced mycobacterial burden in vivo, and in a murine rifampicin-resistant infection model, pretomanid plus the engineered strain achieved greater bacterial reduction than either monotherapy.

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