Delphine Cormontagne

Microbiologie de l’alimentation au service de la santé

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Nalini Ramarao

Microbiologie de l’alimentation au service de la santé

Seav‐Ly Tran

Microbiologie de l’alimentation au service de la santé

Jasmina Vidić

Microbiologie de l’alimentation au service de la santé

Gwenaëlle André

Université Paris-Saclay

Solène Albert

Mathématiques et Informatique Appliquées du Génome à l'Environnement

Samantha Samson

Mathématiques et Informatique Appliquées du Génome à l'Environnement

Rozenn Dervyn

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Gwenaëlle André-Leroux

Université Paris-Saclay

Jean‐François Nicolas

Centre International de Recherche en Infectiologie

SL. Tran

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

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Université Paris-Saclay

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Microbiologie de l’alimentation au service de la santé

Centre National de la Recherche Scientifique

Inserm

AgroParisTech

Mathématiques et Informatique Appliquées du Génome à l'Environnement

Assistance Publique – Hôpitaux de Paris

Interdisciplinarité en Santé Publique Interventions et Instruments de mesure complexes – Région Est

Institut National de la Recherche Agronomique

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Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic Bacillus cereus Strains

Toxins (2020)

Seav‐Ly Tran Delphine Cormontagne Jasmina Vidić Gwenaëlle André Nalini Ramarao

The emergence of B. cereus as an opportunistic food-borne pathogen has intensified the need to distinguish strains of public health concern. The heterogeneity of the diseases associated with B. cereus infections emphasizes the versatility of these bacteria strains to colonize their host. Nevertheless, the molecular basis of these differences remains unclear. Several toxins are involved in virulence, particularly in gastrointestinal disorders, but there are currently no biological markers able to differentiate pathogenic from harmless strains. We have previously shown that CwpFM is a cell wall peptidase involved in B. cereus virulence. Here, we report a sequence/structure/function characterization of 39 CwpFM sequences, chosen from a collection of B. cereus with diverse virulence phenotypes, from harmless to highly pathogenic strains. CwpFM is homology-modeled in silico as an exported papain-like endopeptidase, with an N-terminal end composed of three successive bacterial Src Homology 3 domains (SH3b1–3) likely to control protein–protein interactions in signaling pathways, and a C-terminal end that contains a catalytic NLPC_P60 domain primed to form a competent active site. We confirmed in vitro that CwpFM is an endopeptidase with a moderate peptidoglycan hydrolase activity. Remarkably, CwpFMs from pathogenic strains harbor a specific stretch of twenty residues intrinsically disordered, inserted between the SH3b3 and the catalytic NLPC_P60 domain. This strongly suggests this linker as a marker of differentiation between B. cereus strains. We believe that our findings improve our understanding of the pathogenicity of B. cereus while advancing both clinical diagnosis and food safety.

Cereus

10.3390/toxins12090593

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Mfd, a protein involved in B. cereus virulence and a new target for the development of innovative antimicrobials

HAL (Le Centre pour la Communication Scientifique Directe) (2023)

Delphine Cormontagne

Cereus

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The sequence of the universal bacterial DNA repair protein Mfd dictates the pathogenicity of Bacillus cereus strains

HAL (Le Centre pour la Communication Scientifique Directe) (2021)

Delphine Cormontagne Seav‐Ly Tran Samantha Samson Gwenaëlle André-Leroux Solène Albert

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The structure of bacterial Mfd dictates the pathogenicity in Bacillus cereus

HAL (Le Centre pour la Communication Scientifique Directe) (2021)

Gwenaëlle André-Leroux Samantha Samson Delphine Cormontagne Seav‐Ly Tran Solène Albert

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Bacillus cereus Induces Severe Infections in Preterm Neonates: Implication at the Hospital and Human Milk Bank Level

Toxins (2021)

Delphine Cormontagne Virginie Rigourd Jasmina Vidić Francesco Rizzotto Emmanuelle Bille

Human breast milk (HBM) is a source of essential nutrients for infants and is particularly recommended for preterm neonates when their own mother's milk is not available. It provides protection against infections and decreases necrotizing enterocolitis and cardiovascular diseases. Nevertheless, HBM spoilage can occur due to contamination by pathogens, and the risk of a shortage of HBM is very often present.

10.3390/toxins13020123

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An anti-virulence drug targeting the evolvability protein Mfd protects against infections with antimicrobial resistant ESKAPE pathogens

bioRxiv (Cold Spring Harbor Laboratory) (2024)

SL. Tran Lucie Lebreuilly Delphine Cormontagne Séverine Samson TB. Tô

Abstract The increased incidence of antibiotic resistance and declining discovery of new antibiotics have created a global health crisis, especially for the treatment of infections caused by Gram-negative bacteria. Here, we identify and characterize a molecule, NM102, that displays antimicrobial activity exclusively in the context of infection. NM102 inhibits the activity of the non-essential Mutation Frequency Decline (Mfd) protein by competing with ATP binding to its active site. Inhibition of Mfd by NM102 sensitizes pathogenic bacteria to the host immune response and blocks infections with clinically- relevant Klebsiella pneumoniae and Pseudomonas aeruginosa , without inducing host toxicity. Finally, NM102 inhibits the function of Mfd as a mutation and evolvability factor, thus reducing the bacterial capacity to develop antimicrobial resistance. These data provide a potential roadmap to expand the arsenal of drugs to combat antimicrobial resistance. Highlight NM102 is a “first in class” molecule specifically targeting the active site of the bacterial Mfd protein NM102 has a new mode of action: it inhibits Mfd function during immune stress response NM102 also inhibits Mfd evolvability function and thereby decreases bacterial resistance to known antibiotics NM102 effectively treats Gram-negative infections in animal models NM102 is efficient against clinically relevant resistant bacteria and provides an increased efficacy in combination with the β-lactam meropenem

Evolvability

Virulence factor

10.1101/2024.01.22.576688

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Identification of a New Pathogenicity Island Within the Large pAH187_270 Plasmid Involved in Bacillus cereus Virulence

Frontiers in Cellular and Infection Microbiology (2022)

Rozenn Dervyn Devon Kavanaugh Delphine Cormontagne Benjamin Glasset Nalini Ramarao

Objectives Bacillus cereus is responsible for food poisoning and rare but severe clinical infections. The pathogenicity of B. cereus strains varies from harmless to lethal strains. The objective of this study was to characterize three B. cereus isolates isolated from the same patient and identify their virulence potentials. Methods Three isolates of B. cereus were isolated from various blood samples from a patient who developed sepsis following a central venous catheter infection. The three isolates were compared by WGS, genotyping and SNP analysis. Furthermore, the isolates were compared by phenotypical analysis including bacterial growth, morphology, germination efficacy, toxin production, antibiotic susceptibility and virulence in an insect model of infection. Results According to WGS and genotyping, the 3 isolates were shown to be identical strains. However, the last recovered strain had lost the mega pAH187_270 plasmid. This last strain showed different phenotypes compared to the first isolated strain, such as germination delay, different antibiotic susceptibility and a decreased virulence capacity towards insects. A 50- kbp region of pAH187_270 plasmid was involved in the virulence potential and could thus be defined as a new pathogenicity island of B. cereus . Conclusions These new findings help in the understanding of B. cereus pathogenic potential and complexity and provide further hints into the role of large plasmids in the virulence of B. cereus strains. This may provide tools for a better assessment of the risks associated with B. cereus hospital contamination to improve hygiene procedure and patient health.

Cereus

10.3389/fcimb.2021.788757

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Citations (2)