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Updated: Aug 19, 2026

Separating Bacteria by Capsule Amount Using a Discontinuous Density Gradient
Published on: January 7, 2019
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.
Abstract:
Carbapenem-resistant Enterobacteriaceae (CRE) are life-threatening multidrug-resistant superbugs with severely limited treatment options, highlighting the urgent need for next-generation therapeutics that employ novel mechanisms of action. Microbiome-based therapies have emerged as a promising alternative, with several development pipelines actively progressing. In this study, a comprehensive evaluation of efficacy and safety based on mechanistic evidence is critical for the optimal selection of therapeutic candidate strains. So, we evaluated Lactobacillus and Bacillus candidate strains for activity against CRE, assessing their efficacy and safety in the context of mechanistic insights. Cell-free supernatants derived from these strains exhibited dose-dependent growth inhibition and time-dependent bactericidal activity against carbapenem-resistant Klebsiella pneumoniae. All candidate strains exhibited acceptable safety profiles with no hemolytic activity, although bile salt deconjugation and antibiotic susceptibility patterns varied by strain. Mechanistic analyses revealed that treatment with cell-free supernatants significantly reduced the production of capsular polysaccharide (CPS) and downregulated the CPS biosynthesis-related gene galF, thereby enhancing susceptibility to human serum killing. Additionally, a strong correlation was observed between antibacterial potency and CPS suppression, and two relatively superior candidate strains were prioritized based on their dual functional advantages. Collectively, these findings provide a robust mechanistic rationale for strain prioritization and support the strategic advancement of capsule suppression-based microbiome therapeutics for controlling CRE infections into preclinical and clinical development.
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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