Reactive Oxygen Species-Dependent Innate Immune Mechanisms Control Methicillin-Resistant Staphylococcus aureus Virulence in the Drosophila Larval Model
| Autor: | Mathieu Coureuil, Laurence Arbibe, Daniel Euphrasie, Louison Lallemant, Clémence Bouvier, Xiongqi Ding, Elodie Ramond, Alain Charbit, Anne Jamet, Xiangyan He |
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| Přispěvatelé: | Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Charbit, Alain |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Pore Forming Cytotoxic Proteins Staphylococcus aureus Virulence medicine.disease_cause Microbiology [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity intestinal infection 03 medical and health sciences Duox Shigella flexneri Immune system [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Virology medicine Animals Antimicrobial peptide production [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity 030304 developmental biology 0303 health sciences Innate immune system biology 030306 microbiology catalase Gene Expression Regulation Bacterial Staphylococcal Infections biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification Methicillin-resistant Staphylococcus aureus [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Immunity Innate QR1-502 3. Good health virulence Disease Models Animal Drosophila melanogaster Salmonella enterica Larva Host-Pathogen Interactions [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Reactive Oxygen Species Research Article gastrointestinal infection |
| Zdroj: | mBio mBio, American Society for Microbiology, 2021, 12 (3), pp.e00276-21. ⟨10.1128/mBio.00276-21⟩ mBio, Vol 12, Iss 3 (2021) mBio, 2021, 12 (3), pp.e00276-21. ⟨10.1128/mBio.00276-21⟩ |
| ISSN: | 2161-2129 2150-7511 |
| Popis: | Antibiotic-resistant Staphylococcus aureus strains constitute a major public health concern worldwide and are responsible for both health care- and community-associated infections. Here, we establish a robust and easy-to-implement model of oral S. aureus infection using Drosophila melanogaster larvae that allowed us to follow the fate of S. aureus at the whole-organism level as well as the host immune responses. Our study demonstrates that S. aureus infection triggers H2O2 production by the host via the Duox enzyme, thereby promoting antimicrobial peptide production through activation of the Toll pathway. Staphylococcal catalase mediates H2O2 neutralization, which not only promotes S. aureus survival but also minimizes the host antimicrobial response, hence reducing bacterial clearance in vivo. We show that while catalase expression is regulated in vitro by the accessory gene regulatory system (Agr) and the general stress response regulator sigma B (SigB), it no longer depends on these two master regulators in vivo. Finally, we confirm the versatility of this model by demonstrating the colonization and host stimulation capabilities of S. aureus strains belonging to different sequence types (CC8 and CC5) as well as of two other bacterial pathogens, Salmonella enterica serovar Typhimurium and Shigella flexneri. Thus, the Drosophila larva can be a general model to follow in vivo the innate host immune responses triggered during infection by human pathogens. IMPORTANCE The pathogenicity of methicillin-resistant S. aureus (MRSA) strains relies on their ability to produce a wide variety of tightly regulated virulence factors. Current in vivo models to analyze host-pathogen interactions are limited and difficult to manipulate. Here, we have established a robust and reliable model of oral S. aureus infection using Drosophila melanogaster larvae. We show that S. aureus stimulates host immunity through the production of reactive oxygen species (ROS) and antimicrobial peptide (AMP) and that ROS potentialize AMP gene expression. S. aureus catalase plays a key role in this complex environment and acts in vivo independently from SigB and Agr control. We propose that fly larvae can provide a general model for studying the colonization capabilities of human pathogens. |
| Databáze: | OpenAIRE |
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