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OM-89 may curb postantibiotic E coli regrowth
Lysosomal activation and increased intracellular antibiotic accumulation accompanied reduced bacterial regrowth across mouse and human bladder epithelial models.
To investigate the effects of OM-89 on the regrowth of uropathogenic Escherichia coli (UPEC) following antibiotic treatment.
Approach:
Experimental Design: Mouse and human bladder organoids and differentiated epithelial monolayers were used to assess the impact of OM-89 on bacterial clearance and regrowth.
Treatment Regimens: OM-89 was administered either 72 hours prior to infection or continuously for 72 hours prior to infection and throughout the study.
Functional Assessments: Bacterial clearance during antibiotic treatment and regrowth post-antibiotic withdrawal were measured, along with intracellular bacterial burden and lysosomal function.
Transcriptomic Profiling: Gene expression changes were analyzed to identify pathways affected by OM-89.
Key Findings:
OM-89 reduced bacterial burden during antibiotic treatment and decreased postantibiotic regrowth under all exposure regimens.
The strongest effect on regrowth reduction occurred when OM-89 was present during antibiotic treatment.
Increased intracellular accumulation of antibiotics was observed in differentiated mouse bladder epithelial cells treated with OM-89.
OM-89 enhanced lysosomal acidification and protease activity, which were necessary for its antimicrobial effects.
In human bladder organoids, OM-89 significantly reduced bacterial regrowth after antibiotic treatment.
Limitations:
OM-89 was applied directly to bladder cultures, differing from its oral administration in clinical practice.
The interaction of epithelial responses with systemic and immune-mediated effects was not addressed.
Fluorescence-based measurements may not distinguish between luminal and intracellular bacteria, potentially masking early effects.
