Estradiol-Induced Modulation of Clindamycin Susceptibility in Mono- and Dual-Species Biofilms of Lactobacillus gasseri and Cutibacterium acnes: An In Vitro Model Study

This pilot study investigated the effects of estradiol and clindamycin on mono- and dual-species biofilms of selected reference and clinical isolates of Lactobacillus gasseri and Cutibacterium acnes, including one vaginal isolate of C. acnes. Our findings demonstrate complex, strain-dependent effects of both compounds and their combinations. Estradiol inhibited biofilm formation in L. gasseri strains but exhibited divergent impacts on C. acnes isolates, stimulating the skin-derived strain while suppressing the vaginal isolate. The observation that pre-adsorbed estradiol tended to enhance its biological activity is consistent with, though does not prove, the hypothesis of a direct hormonal interaction with the bacterial cell envelope. Crucially, estradiol modulated the susceptibility of both species to clindamycin. At the working concentration selected, clindamycin susceptibility varied considerably between strains, with the antibiotic stimulating biofilm growth in skin-derived C. acnes HM514 biofilms. In dual-species communities, an apparent inversion of clindamycin activity was observed, suggesting that estradiol may alter antibiotic efficacy in a manner dependent on community composition and strain identity. Furthermore, while transcriptional changes in bacteriocin genes were evident under hormonal and antibiotic pressure, these shifts did not consistently correlate with observed phenotypic antagonistic activity. These results underscore the limitations of traditional mono-species assays and highlight the importance of considering hormonal background, community context, and the substantial phenotypic variability among individual microbial isolates when evaluating antimicrobial interventions.