Biology subjects

Pakkir Shah, A. K.

Publications and source records attributed to Pakkir Shah, A. K..

3 recordsLinked to original sources

bioRxiv2026

A Functional Metabolomics Framework to Track Microbiome Drug Metabolism

Understanding how gut microbes transform drugs, and how this influences microbiome composition and function, remains a key question to better understand the efficacy and side effects of pharmaceuticals. To accelerate the discovery of microbiome-derived drug metabolites, we developed a functional metabolomics workflow that combines the use of synthetic microbial communities (SynComs) with a time-series resolved molecular networking approach and advanced computational metabolite annotation. We demonstrate how this framework can be used to illuminate chemical transformation dynamics in a gut SynCom (Com20) with 50 clinical drugs. Our results highlight a multitude of drug metabolites, including multi-step metabolic cascades, some of which correlated to shifts in microbial taxa, suggesting functional links between microbiome composition and biochemical transformations. Our computational data analysis workflow is publicly available through the GNPS2 ecosystem at chemprop.gnps2.org, which can be used to prioritize biotransformations and other (bio)chemical reactions in various biological and abiotic systems.

systems biology↗

bioRxiv2025

The offensive role of the Bacillus extracellular matrix in driving metabolite-mediated dialogue and adaptive strategies with pathogenic fungi

Bacterial{square}fungal interactions have traditionally been attributed to secondary metabolites, but the role of the bacterial extracellular matrix (ECM) in shaping these relationships has remained unclear. Here, we demonstrate that the ECM protein TasA is a key mediator in the antagonistic interaction between Bacillus subtilis and Botrytis cinerea. TasA enables Bacillus to tightly adhere to fungal hyphae, disrupts the {beta}-glucan layer, and compromises fungal cytoskeletal integrity synergistically with fengycin, which causes cytological damage. Additionally, TasA acts as a carrier for bacillaene, amplifying its fungistatic activity. In response, B. cinerea mounts a multifaceted defense, enzymatically degrading fengycin, producing antibacterial oxylipins, and activating adaptive programs such as hyphal branching and chlamydospore formation. Our findings reveal the previously unrecognized role of ECM components in fungal suppression and the modulation of fungal adaptive responses. This study reveals the complex interplay between microbial aggression and defense, providing new insights into the ecological dynamics of microbial competition and coexistence.

microbiology↗

bioRxiv2023

Cyclo(Pro-Tyr) elicits conserved cellular damage in fungi by targeting the ATPase Pma1 in plasma membrane domains

Bioactive metabolites play a crucial role in shaping interactions among diverse organisms. In this study, we identified cyclo(Pro-Tyr), a metabolite produced by Bacillus velezensis, as a potent inhibitor of Botrytis cinerea and Caenorhabditis elegans, two potential cohabitant eukaryotic organisms. Based on our investigation, cyclo(Pro-Tyr) disrupts plasma membrane polarization, induces oxidative stress and increases membrane fluidity, which compromises fungal membrane integrity. These cytological and physiological changes induced by cyclo(Pro-Tyr) may be triggered by the destabilization of membrane microdomains containing the [H+]ATPase Pma1. In response to cyclo(Pro-Tyr) stress, fungal cells activate a transcriptomic and metabolomic response, which primarily involves lipid metabolism and Reactive Oxygen Species (ROS) detoxification, to mitigate membrane damage. This similar response occurs in the nematode C. elegans, suggesting that cyclo(Pro-Tyr) universally targets eukaryotic cellular membranes.

microbiology↗