Biology subjects

Perez-Garcia, A.

Publications and source records attributed to Perez-Garcia, A..

5 recordsLinked to original sources

bioRxiv2026

Explainable AI for end-to-end pathogen target discovery and molecular design

Drug discovery is limited by target identification, a major bottleneck in antimicrobial development and in combating emerging fungicide resistance. We present APEX (Attention-based Protein EXplainer), an explainable AI framework for cross-species, proteome-scale target discovery and pocket-guided molecular design. APEX combines ESM-2 embeddings, GAT, and a MLP to train pathogen-specific essentiality predictors (APEX-Tar) alongside a universal druggability model (APEX-Drug). Attention maps and GNNExplainer-derived subgraphs highlight residues driving predictions, enabling direct conditioning of structure-based diffusion models for inhibitor generation. APEX-Tar identifies key residues in known fungal targets and nominates new candidates, including adenylosuccinate lyase (ADSL) in fungi and the bacterial adhesin YadV. APEX-Drug recapitulates established fungicide binding sites, guides the design of ADSL inhibitors exploiting a fungal-specific active-site residue, and uncovers in YadV a previously undescribed pocket distinct from known pilicide sites. Together, APEX provides a kingdom-agnostic, explainable pipeline for target prioritization and guided molecular design, accelerating the search for next-generation antimicrobials.

bioinformatics↗

bioRxiv2025

Characterization of BvlzGluc, a Novel Antifungal beta-Glucanase from Bacillus velezensis, with Potential Agricultural and Industrial Applications

{beta}-glucanases play a critical role in degrading {beta}-glucans, which are essential components of fungal cell walls that maintain fungal structure and physiology. This study characterizes BvlzGluc, a novel {beta}-glucanase produced by Bacillus velezensis CECT 8237, which has potent antifungal properties. BvlzGluc specifically targets the {beta}-glucan layer of Botrytis cinerea, causing significant structural malformations, impaired fungal development, and reduced virulence. These effects weaken the fungal cell wall, increasing its susceptibility to environmental stress and reducing its capacity to infect host plants. Notably, BvlzGluc is a noncanonical {beta}-glucanase belonging to glycoside hydrolase family 16 (GH16) but presents unique structural features that distinguish it from typical members of this family, suggesting potential reclassification. Its physicochemical stability and simple structural design increase its suitability for scalable production, positioning it as a promising candidate for agricultural and industrial applications requiring efficient {beta}-glucan degradation. This work builds on previous studies of microbial antifungal mechanisms, providing new insights into bacterial-fungal interactions and reinforcing the potential of bacterial enzymes in sustainable pathogen management and advancing biotechnological innovations.

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↗

bioRxiv2021

Mutualistic interactions between B. subtilis and seeds dictate plant development

A tightly coordinated developmental program controls precise genetic and metabolic reprogramming that dictates efficient transition of the seeds from dormancy to metabolically active seedlings. Beneficial microbes are known to stimulate the germination of the seeds or adaptation of the seedlings; however, investigations of exact mechanisms mediating these interactions and the resulting physiological responses of the plants are only beginning. Bacillus subtilis is commonly detected in the plant holobiont and belongs to the group of microbes that provide multifaceted contribution to the health of the plants. The present study demonstrated that B. subtilis triggered genetic and physiological responses in the seeds that determined subsequent metabolic and developmental status of adult plants. Chemically diverse extracellular matrix of Bacillus was demonstrated to structurally cooperate in bacterial colonization of the seed storage tissues. Additionally, an amyloid protein and fengycin, which are two components of the extracellular matrix, targeted the oil bodies of the seed endosperm, provoking changes in lipid metabolism or accumulation of glutathione-related molecules that stimulated two different plant growth programs: the development of seed radicles or overgrowth and immunization of adult plants. We propose this mutualistic interaction is conserved in Bacilli and plant seeds containing storage oil bodies.

microbiology↗

bioRxiv2019

Dual functionality of the TasA amyloid protein in Bacillus physiology and fitness on the phylloplane

Bacteria can form biofilms that consist of multicellular communities embedded in an extracellular matrix (ECM). Previous studies have demonstrated that genetic pathways involved in biofilm formation are activated under a variety of environmental conditions to enhance bacterial fitness; however, the functions of the individual ECM components are still poorly understood. In Bacillus subtilis, the main protein component of the ECM is the functional amyloid TasA. In this study, we demonstrate that beyond their well-known defect in biofilm formation,{Delta} tasA cells also exhibit a range of cytological symptoms indicative of excessive cellular stress, including DNA damage accumulation, changes in membrane potential, higher susceptibility to oxidative stress, and alterations in membrane dynamics. Collectively, these events can lead to increased programmed cell death in the colony. We show that these major physiological changes in{Delta} tasA cells are likely independent of the structural role of TasA during amyloid fiber formation in the ECM. The presence of TasA in cellular membranes, which would place it in proximity to functional membrane microdomains, and mislocalization of the flotillin-like protein FloT in{Delta} tasA cells, led us to propose a role for TasA in the stabilization of membrane dynamics as cells enter stationary phase. We found that these alterations caused by the absence of TasA impair the survival, colonization and competition of Bacillus cells on the phylloplane. Taken together, our results allow the separation of two complementary roles of this functional amyloid protein: i) structural functions during ECM assembly and interactions with plants, and ii) a physiological function in which TasA, via its localization to the cell membrane, stabilizes membrane dynamics and supports more effective cellular adaptation to environmental cues.

microbiology↗