Biology subjects

Molina Panadero, I.

Publications and source records attributed to Molina Panadero, I..

3 recordsLinked to original sources

bioRxiv2026

OmpA controls intracellular survival of Acinetobacter baumannii through TFEB activation and lysosomal remodeling

Acinetobacter baumannii is a high-priority multidrug-resistant pathogen that survives within host cells by hijacking intracellular defense pathways. Here, we identify a previously unrecognized signaling axis linking bacterial invasion to host lysosomal regulation. We show that A. baumannii activates calcium-independent phospholipase A2 (iPLA2), leading to increased lysophosphatidylcholine (LPC) production and calcium influx through the ORAI1 channel, which together drive activation and nuclear translocation of the lysosomal transcription factor EB (TFEB). Pharmacological inhibition or genetic silencing of iPLA2 or ORAI1 markedly impaired TFEB activation and lysosomal biogenesis. Mechanistically, we demonstrate that this pathway is initiated by the outer membrane protein A (OmpA), which promotes bacterial invasion and enhances iPLA2 activity, LPC production, and downstream TFEB signaling. Despite induction of lysosomal biogenesis, A. baumannii persists intracellularly by producing ammonia and alkalinizing the lysosomal environment, thereby counteracting host antibacterial activity. In vivo, infection induces activation of HLH-30, the TFEB ortholog, in Caenorhabditis elegans in an OmpA-dependent manner. Together, our finding define an OmpA-iPLA2-LPC-ORAI1-TFEB signaling axis that coordinates host lipid and calcium signaling with lysosomal responses, while revealing a bacterial counterstrategy that promotes intracellular survival.

microbiology↗

bioRxiv2025

Discovery of a novel antibiotic class targeting the enolase of Acinetobacterbaumannii

High-throughput screening studies provide an additional approach to discovering repurposed drugs for antimicrobial treatments. In this work, we report the identification of ENOblock, an anticancer drug, as a novel antibiotic class. We computationally and experimentally validated that ENOblock synergizes with colistin, the last resort antibiotic, the colistin. Additionally, we identified enolase as the potential bacterial target for ENOblock. The in silico and in vitro antibacterial activity of ENOblock translated into potent in vivo efficacy in animal infection model. Collectively, the preclinical data support the selection of ENOblock as a promising candidate for antimicrobial development, with the potential to address the urgent threat of infections caused by Acinetobacter baumannii.

microbiology↗

bioRxiv2024

Antibacterial activity of tamoxifen derivatives against methicillin-resistant Staphylococcus aureus

The present work aimed to discover new tamoxifen derivatives with antimicrobial potential, particularly targeting methicillin-resistant Staphylococcus aureus (MRSA). The MIC of 22 tamoxifen derivatives was determined against S. aureus reference and MRSA strains, using microdilution assays. The antibacterial effects of selected tamoxifen derivatives against MRSA (USA7) were assessed through bacterial growth assays. Bacterial membrane permeability and molecular docking assays were performed. The MIC of the tamoxifen derivatives against MRSA ranged from to 16 to >64 g/mL. Bacterial growth assays demonstrated that tamoxifen derivatives 2, 5, and 6 reduced dose-dependently the growth of the USA7 strain. Moreover, treatment of MRSA with derivatives 2 and 5 resulted in increased membrane permeabilization without being the cell wall their molecular target. These data suggest that tamoxifen derivatives exhibit antibacterial activity against MRSA, potentially broadening the spectrum of available drug treatments for combating antimicrobial-resistant Gram-positive bacteria. ImportanceThe development of new antimicrobial therapeutic strategies requires immediate attention to avoid the tens of millions of deaths predicted to occur by 2050 as a result of multidrug-resistant (MDR) bacterial infections. In this study, we assessed the antibacterial activity of 22 tamoxifen derivatives against methicillin-resistant Staphylococcus aureus (MRSA). We found that three tamoxifen derivatives exhibited antibacterial activity against MRSA clinical isolats, presenting MIC50 values between 16 and 64 g/mL and reducing bacterial growth over 24 h. Additionally, this antibacterial activity for two of the derivatives was accompanied by increased membrane permeability of MRSA. Our results suggest that tamoxifen derivatives might be used as a potential therapeutic alternative for treating MRSA strains in an animal model of infection.

microbiology↗