Benzodioxane-Benzamides Targeting Bacterial Cell Division Protein FtsZ Potentially Disrupt SlmA-Mediated Nucleoid Occlusion and Reversible Biomolecular Condensation

Authors

Marta Sobrinos-Sanguino
Inés Barros-Medina
Lorenzo Suigo
Alessia Lanzini
Ermanno Valoti
William Margolin
Valentina Straniero
Begoña Monterroso
Silvia Zorrilla

Language

English

Publication Date

12-1-2025

Journal

International Journal of Biological Macromolecules

DOI

10.1016/j.ijbiomac.2025.148516

PMID

41138864

PMCID

PMC12693692

PubMedCentral® Posted Date

12-11-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

New strategies are urgently needed against antimicrobial resistance, a major health threat, and the different mechanisms regulating the bacterial cell division machinery offer multiple opportunities for developing novel therapeutics. FtsZ, an essential protein of this process, is targeted by multiple small molecules, and benzodioxane-benzamides (BDOBs) are among the most potent inhibitors in several bacterial species. BDOBs mechanisms are however poorly understood, particularly their impact on FtsZ's interplay with partners and ability to assemble phase-separated biomolecular condensates potentially involved in stress sensing. We show that certain BDOBs shielded FtsZ against depolymerization induced by the nucleoprotein complexes of SlmA, which inhibit Z-ring formation near the nucleoid. In crowding cytomimetic conditions, BDOBs disrupted the canonical interconversion between FtsZ-SlmA condensates and polymers in response to GTP levels. Our results strongly suggest that BDOBs interfere with normal regulation of Z-ring assembly by antagonists such as SlmA that protect important cellular structures like the nucleoid. Specifically, BDOBs may reduce the susceptibility of FtsZ polymers to SlmA and impair biomolecular condensates reassembly. We propose that fine tuning of the equilibrium between FtsZ polymers and biomolecular condensates is important for spatial regulation of Z-rings and stress resistance, and this equilibrium is subverted by BDOBs.

Keywords

Cytoskeletal Proteins, Bacterial Proteins, Cell Division, Benzamides, Dioxanes, Escherichia coli Proteins, Escherichia coli, Carrier Proteins

Published Open-Access

yes

Recommended Citation

Sobrinos-Sanguino, Marta; Barros-Medina, Inés; Suigo, Lorenzo; et al., "Benzodioxane-Benzamides Targeting Bacterial Cell Division Protein FtsZ Potentially Disrupt SlmA-Mediated Nucleoid Occlusion and Reversible Biomolecular Condensation" (2025). Faculty, Staff and Student Publications. 6239.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6239