Ivo Gomperts Boneca

Website: https://research.pasteur.fr/en/team/biology-and-genetics-of-bacterial-cell-wall/
ORCID: 0000-0001-8122-509X 
Twitter: @ivo_boneca

Our team studies the cell wall and cell envelope of bacteria with the aim to better understand how these structures are assembled during cell growth and division, determine the cell shape of bacteria and how they mediate cell-host communication. We have used a combination of structural biology, biochemistry and bacterial cell biology to dissect how some of the proteins involved in the assembly and maturation process of the cell envelope function at the enzymatic level as well as in protein complexes in two model bacteria Helicobacter pylori and Neisseria meningitidis.

We also search for novel proteins involved in these processes by combining unbiased screens of mutant libraries, Omics approaches and genomic analysis. In particular, we are interested in studying the process of morphological transition, both at the cellular level (ex: in H. pylori) and at the evolutionary level (ex: in Neisseria sp.). Our studies have allowed us to identify multiple new “Achilles heels” for which we already developed or will develop screening assays to identify inhibitors of cell wall biogenesis and cell envelope synthesis and assembly that may contribute to the development of novel antibiotics.

Besides its essential role for cell viability, the cell wall and cell envelope are in contact with the environment and, in particular, with the host. Many cell wall and cell envelope structures are unique to bacteria and are sensed by receptors of the innate immune system. These microbial-associated molecular patterns (MAMPs) mediate an important dialogue between bacteria and the host both during health and disease. We study how different commensal bacteria mediate beneficial physiological effects on the host via cell wall components. These effects range from local effects in the gut to systemic effects in distant tissues of the body such as the brain or tumors.

Pathogenic bacteria subvert these mechanisms of communication to their advantage to support the ability of disseminating and colonizing host tissues. For example, Leptospira interrogans, the agent of leptospirosis, a neglected infectious disease, has developed several distinct mechanisms to escape sensing by multiple innate immune receptors.

We will pursue studies on how cell wall components shape host physiology. In particular, we will elucidate the molecular mechanism behind the transport of these components across the gut and their systemic dissemination and determine how these processes are altered in chronic inflammatory diseases. In parallel, we will continue studies to understand how pathogens subvert the innate immune system and use this knowledge to develop host-directed therapies boosting the immune response to improve prophylaxis, antibiotic treatments and vaccination efficacy.

Top 5 publications

1. Gabanyi I, G Lepousez, R Wheeler, A Vieites-Prado, A Nissant, S Wagner, C Moigneu, S Dulauroy, S Hicham, B Polomack, F Verny, P Rosenstiel, N Renier, IG Boneca, G Eberl, PM Lledo. (2022)
Bacterial sensing via neuronal Nod2 regulates appetite and body temperature.
Science. 376(6590):eabj3986.

2. Bonhomme D, I Santecchia, F Vernel-Pauillac, M Caroff, P Germon, G Murray, B Adler, IG Boneca, C Werts. (2020)
Leptospiral LPS escapes mouse TLR4 internalization and TRIF-associated antimicrobial responses through O antigen and associated lipoproteins.
PLoS Pathog. 16(8):e1008639

3. Williams AH, R Wheeler, A-E Deghmane, I Santecchia, RE Schaub, S Hicham, M Moya Nilges, C Malosse, J Chamot-Rooke, A Haouz, JP Dillard, WP Robins, M-K Taha, IG Boneca. (2020)
Defective lytic transglycosylase disrupts cell morphogenesis by hindering cell wall de-O-acetylation in N. meningitidis.
eLife. 51247.

4. Nozeret K, A Boucharlat, F Agou, N Buddelmeijer. (2019)
A sensitive fluorescence-based assay to monitor enzymatic activity of the essential integral membrane protein Apolipoprotein N-acyltransferase.
Sci Rep. 9:15978.

5. Gasiorowski E, R Auger, X Tian, S Hicham, C Ecobichon, S Roure, MV Douglass, M Stephen Trent, D Mengin-Lecreulx, T Touzé, IG Boneca. (2019)
HupA, the main undecaprenyl pyrophosphate and phosphatidylglycerol phosphate phosphatase in Helicobacter pylori is essential for colonization of the stomach.
PLoS Pathog. 15(9):e1007972.

Dernières publications sur HAL :