HEИндивидуална стипендия2023–2025

SLYDIV · Unveiling the molecular coordination between the cell division machinery and S-layer biogenesis in Bacillus anthracis

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период
2023-09-01 → 2025-08-31
Финансиране от ЕС
175 920 €
Участници
1
Схема
HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Бактериалните повърхностни слоеве (S-слоеве) и начинът, по който те се изграждат при делене на клетките, се изучават чрез примера на Bacillus anthracis. Разбирането на тези механизми помага за разработването на нови антимикробни терапии и приложения в биоинженерството.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Unveiling the molecular coordination between the cell division machinery and S-layer biogenesis in Bacillus anthracis

The SLYDIV project was designed to address a fundamental question in microbiology: how do bacteria coordinate the assembly of their surface layers (S-layers) with cell growth and division? S-layers are proteinaceous crystalline arrays that coat the surface of many bacteria and archaea, playing critical roles in structural integrity, environmental resilience, and host-pathogen interactions. Despite their ubiquity, the molecular mechanisms governing S-layer biogenesis and their integration with the bacterial cell cycle remain poorly understood. This knowledge gap is particularly relevant in the context of antimicrobial resistance and the need for novel therapeutic strategies. In pathogens such as Bacillus anthracis, the S-layer is essential for virulence and cell envelope stability, making it a promising target for antimicrobial development. Similarly, in industrially relevant species like Corynebacterium glutamicum, understanding S-layer dynamics offers opportunities for synthetic biology and bioengineering applications. The original objectives of the SLYDIV project were to: 1. Determine the atomic structure of the S-layer protein in B. anthracis. 2. Investigate the spatial and temporal dynamics of S-layer assembly, particularly its coordination with polar growth. 3. Unveil the molecular coordination between the divisome and S-layer biogenesis These objectives were pursued using a multidisciplinary approach combining cryo-electron microscopy, X-ray crystallography, microbiology, and live-cell imaging. The project has yielded significant advances, including the first complete atomic model of the B. anthracis S-layers Sap and EA1, the discovery of polar S-layer assembly in C. glutamicum, and the development of a modular S-layer engineering platform. In addition to these planned outcomes, the project also led to an unexpected but highly valuable collaboration that expanded the scientific scope. In partnership with colleagues at the VIB-VUB Center for Structural Biology, I contributed to the discovery and characterization of a novel class of protein nanofibers, A-ENA (alpha-helical endospore appendages) produced by Bacillus thuringiensis. These fibers form a robust extracellular matrix that clusters spores and parasporal bodies (PSBs), enhancing the insecticidal efficacy of this biopesticide. This work, although not part of the original SLYDIV objectives, provided a unique opportunity to deepen my expertise in bacterial surface structures and their functional roles in pathogenesis and biotechnology. The broader impact of the SLYDIV project lies in its contribution to EU policy priorities in health, biosecurity, and sustainable agriculture. By advancing our understanding of bacterial surface architecture and developing tools for its manipulation, the project supports the development of next-generation antimicrobials, bio-based production systems, and environmentally friendly pest control strategies. The integration of fundamental research with translational potential exemplifies the MSCA mission to foster scientific excellence and societal impact across Europe.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Many bacteria possess a paracrystaline protein coat named the S-layer. S-layers cover the entire cell surface and are involved in protection, virulence, cell-shape maintenance and communication. Lattice integrity is essential for S-layer function, meaning that its assembly must be intimately coordinated with cell growth and division. Some studies have reported that S-layer biogenesis co-localizes with peptidoglycan (PG) synthesis, however, the underlying molecular mechanisms remain unknown. Here, I will investigate the molecular regulatory network that orchestrates S-layer assembly, cell division and PG synthesis in the human pathogen Bacillus anthracis, where S-layer defects render the bacterium avirulent, making this ultrastructure an attractive therapeutic target.In the SLYDIV project I will 1) structurally and functionally compare Sap and EA1, the exponential and stationary phase S-layer proteins of B. anthracis 2) follow their in vivo assembly using time-resolved labelling and fluorescent microscopy and 3) uncovering the molecular interactions that couple S-layer assembly with the PG and/or cell division machinery. I will make use of chemicals that selectively target the cell cycle or cell division and monitor localization of S-layer assembly, will use nanobodies that disturb S-layer integrity and monitor the localization of cell wall synthesis, and use my interactomics experience to discover contact partners of S-layer and PG synthesis. Thus, SLYDIV is a multidisciplinary and integrative project that combines structural biology, biophysics, cell imaging, and microbiology. In addition, SLYDIV meets my solid knowledge on bacterial cell division with the host labs’ expertise on S-layer structure and function. The SLYDIV project aims to lead to a major breakthrough in the basic understanding of the regulation of the bacterial cell envelope, while it will pave the way for specific novel molecular therapies against B. Anthracis, a Category A bioterrorist agent.

Оригинален текст от CORDIS (на английски).

Участници

  • VIB VZW · ZWIJNAARDE - GENTКоординаторБелгия

Връзки

Данни: CORDIS, © Европейски съюз