Evaluation of Microbiome Therapeutic Candidates for Carbapenem-Resistant Enterobacteriaceae Associated with Capsule

Ali Atashi1,2, Hoonhee Seo2, Hanieh Tajdozian1,2

  • 1Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31151, Republic of Korea.

Insights

Microbiome therapies show promise against carbapenem-resistant Enterobacteriaceae (CRE). Researchers prioritized Lactobacillus and Bacillus strains by evaluating their ability to suppress bacterial capsules, enhancing susceptibility to immune responses.

Area of Science:

  • Microbiology
  • Microbiome Therapeutics
  • Antimicrobial Resistance

Background:

  • Carbapenem-resistant Enterobacteriaceae (CRE) are critical multidrug-resistant pathogens with limited treatment options.
  • Microbiome-based therapies represent a promising avenue for combating CRE infections.
  • Selecting effective and safe therapeutic strains requires comprehensive mechanistic evaluation.

Purpose of the Study:

  • To evaluate the efficacy and safety of Lactobacillus and Bacillus strains against CRE.
  • To elucidate the mechanisms underlying the antibacterial activity of candidate microbiome therapeutics.
  • To prioritize strains for the development of novel CRE treatments.

Main Methods:

  • Assessed antibacterial activity of cell-free supernatants against carbapenem-resistant Klebsiella pneumoniae.
  • Evaluated safety profiles, including hemolytic activity and bile salt deconjugation.
  • Performed mechanistic analyses, including quantification of capsular polysaccharide (CPS) production and gene expression (galF).

Main Results:

  • Cell-free supernatants demonstrated dose-dependent growth inhibition and time-dependent bactericidal effects against CRE.
  • All tested strains showed acceptable safety profiles; variations noted in bile salt deconjugation and antibiotic susceptibility.
  • Supernatant treatment significantly reduced CPS production and downregulated the galF gene, increasing susceptibility to human serum killing.

Conclusions:

  • A strong correlation exists between antibacterial potency and CPS suppression.
  • Two superior candidate strains were identified based on dual functional advantages (antibacterial activity and CPS suppression).
  • Findings support the advancement of capsule suppression-based microbiome therapeutics for CRE infections.

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