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Engineered Probiotics Protect against Pseudomonas aeruginosa Post Antibiotic Exposure

Siyao Wang1,2, Baoyan Zhang1,2, Shuyi Zhang3,4

  • 1Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Engineering Medicine, Beihang University, Beijing 100083, P. R. China.

ACS Synthetic Biology
|June 10, 2026
PubMed

Insights

Engineered probiotics can restore gut microbiota and immunity after antibiotics. This strategy combines metabolite replenishment and targeted immunization to combat opportunistic infections like Pseudomonas aeruginosa.

Area of Science:

  • Microbiology
  • Immunology
  • Synthetic Biology

Background:

  • Broad-spectrum antibiotics disrupt gut microbiota and mucosal immunity, increasing susceptibility to opportunistic pathogens like Pseudomonas aeruginosa.
  • Limited strategies exist to restore host homeostasis and mucosal immunity during the vulnerable postantibiotic period.

Purpose of the Study:

  • To develop a modular probiotic strategy using engineered Escherichia coli Nissle 1917 (EcN) for metabolite replenishment and antigen-specific mucosal immunization.
  • To evaluate the efficacy of this strategy in restoring immune homeostasis and preventing opportunistic infections post-antibiotic treatment.

Main Methods:

  • Engineered EcN strains to overproduce butyrate for immune restoration.
  • Engineered EcN strains to display Pseudomonas aeruginosa antigens (PcrV or OprL) on outer-membrane vesicles for immunization.
  • Administered engineered EcN strains to antibiotic-exposed mice and challenged with P. aeruginosa.

Main Results:

  • The butyrate-producing EcN restored immune homeostasis, increased pulmonary neutrophils, and enhanced bacterial clearance.
  • Antigen-displaying EcN elicited pathogen-specific mucosal immunity.
  • Both metabolite and immunization modules independently reduced bacterial burden and improved survival; combined administration showed synergistic protection.

Conclusions:

  • A versatile synthetic biology framework using modular engineered probiotics offers a promising approach to combat opportunistic infections.
  • This strategy integrates metabolite replenishment and targeted immunotherapy for enhanced protection against postantibiotic infections.
  • Flexible combination of probiotic modules provides a novel alternative to conventional antibiotic-dependent infection control.
Keywords:
OMV vaccineantibiotic exposurebutyrateengineered probioticsinfection

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