Biology subjects

Lawore, D. C.

Publications and source records attributed to Lawore, D. C..

3 recordsLinked to original sources

bioRxiv2025

Identifying a Vaginal Microbiome-Derived Selective Antibiotic Metabolite via Microbiome Pharmacology Analysis

The vaginal microbiome plays a critical role in maintaining immune and epithelial homeostasis in the female reproductive tract. Bacterial Vaginosis (BV) is deleterious to female health, causing the loss of beneficial Lactobacillus species, overgrowth of anaerobic taxa, changes in vaginal pH, breakdown of protective mucins and epithelial barriers, and activation of the immune system. Treatment with gel-based antibiotics (Metronidazole or Clindamycin) resolves BV for 85% of patients, but 50% of those cases recur, indicating a need to identify strategies for overcoming antibiotic resistance and achieving a more durable response. Here, we developed a systems biology approach termed Microbiome Pharmacology Analysis to characterize the antibiotic potential of vaginal microbes, their metabolites and functions, via computational fusion of human cohort multi-omics and post-drug perturbation transcriptomic profiles. We focused on Clindamycin and Metronidazole as candidate drugs and screened 780 vaginal microbiome-drug mimicry candidates to identify candidate taxa and metabolites with antibiotic potential. We demonstrate experimentally that Lactobacillus crispatus-derived Hydroxyisocaproate (HICA) selectively kills Gardnerella vaginalis and that HICA enhances epithelial barrier integrity in a human vagina-on-a-chip system. Our work demonstrates the first use of Pharmacobiome Analysis, for discovering novel, selective antibiotic metabolites for BV with implications for charting the full pharmacologic potential of the vaginal microbiome.

microbiology↗

bioRxiv2025

Comparative Metabolomic Analysis of Vaginal Microbiota in Planktonic and Biofilm States Unveils Species-Specific Metabolic Signatures

Bacterial vaginosis (BV) affects approximately 29% of women in the U.S., with higher rates among certain demographics and up to 50% recurrence within a year. Besides complications like increased risk of sexually transmitted infections (STIs), pregnancy-related issues, it can negatively impact psychological well-being, leading to discomfort and reduced quality of life. While previous studies have provided insights into the overall metabolomic profile of healthy and diseased vaginal environments, the elucidation of individual microbial metabolite signatures remains limited. Furthermore, given that biofilms exhibit distinct metabolic requirements compared to planktonic cultures, a differential analysis of metabolites in both growth conditions could reveal potential therapeutic targets. This study presents a comprehensive metabolomic analysis and comparison of significant vaginal microbes including Lactobacillus crispatus, Gardenerella vaginalis, and Lactobacillus iners in both planktonic and biofilm growth conditions. Our analysis revealed distinct metabolite production and consumption patterns among different microbes and growth modes. In biofilm cultures, metabolite consumption is influenced by nutrient availability, which in turn regulates the profile of produced metabolites. G. vaginalis demonstrated the ability to form biofilms in various media types. Limited shared metabolic pathways in both biofilm types of G. vaginalis, highlights the unique metabolic processes involved in their formation. Despite L. crispatus suspension and biofilm cultures sharing 142 consumed and 104 produced metabolites, the biofilm culture demonstrated a remarkable metabolic shift. While comparing suspension and biofilm cultures of L. crispatus, L. iners, and G. vaginalis, we found convergence in nutrient utilization, but divergence in metabolic outputs reflecting growth-specific adaptations and underscore the importance of considering the state of existence when studying the vaginal microbiome. This study provides valuable insights into the growth mode-specific metabolic requirements of key vaginal microbes. The findings underscore the potential for leveraging metabolite-mediated microbial cross-talk as a novel therapeutic approach against BV. This avenue of research warrants further investigation, as it could lead to the development of targeted interventions that modulate the vaginal microbiome through metabolic manipulation, potentially offering more effective and personalized treatments for BV.

microbiology↗

bioRxiv2024

Computational Microbiome Pharmacology Analysis Elucidates the Anti-Cancer Potential of Vaginal Microbes and Metabolites

The vaginal microbiomes role in risk, progression, and treatment of female cancers has been widely explored. Yet, there remains a need to develop methods to understand the interaction of microbiome factors with host cells and to characterize their potential therapeutic functions. To address this challenge, we developed a systems biology framework we term the Pharmacobiome for microbiome pharmacology analysis. The Pharmacobiome framework evaluates similarities between microbes and microbial byproducts and known drugs based on their impact on host transcriptomic cellular signatures. Here, we apply our framework to characterization of the Anti-Gynecologic Cancer Vaginal Pharmacobiome. Using published vaginal microbiome multi-omics data from the Partners PrEP clinical trial, we constructed vaginal epithelial gene signatures associated with each profiled vaginal microbe and metabolite. We compared these microbiome-associated host gene signatures to post-drug perturbation host gene signatures associated with 35 FDA-approved anti-cancer drugs from the Library of Integrated Network-based Cellular Signatures database to identify vaginal microbes and metabolites with high statistical and functional similarity to these drugs. We found that Lactobacilli and their metabolites can regulate host gene expression in ways similar to many anti-cancer drugs. Additionally, we experimentally tested our model prediction that taurine, a metabolite produced by L. crispatus, kills cancerous breast and endometrial cancer cells. Our study shows that the Pharmacobiome is a powerful framework for characterizing the anti-cancer therapeutic potential of vaginal microbiome factors with generalizability to other cancers, microbiomes, and diseases.

systems biology↗