Type II fatty acid synthesis pathway and cyclopropane ring formation are dispensable during Enterococcus faecalis systemic infection
| Autor: | Alexandra Gruss, Laurence du Merle, Karine Gloux, Gilles Lamberet, Agnès Fouet, Constantin Hays, Claire Poyart, Clara Lambert, Sophie Brinster |
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| Přispěvatelé: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre national de Référence des Streptocoques (CNR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Bactéries pathogènes à Gram-positif - Biology of Gram-Positive Pathogens, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by funding from the Agence Nationale de la Recherche (ANR-13001038), the Fondation pour la recherche Médicale (DBF20161136769), and from INSERM, CNRS, and Université de Paris., Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Fouet, Agnès |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cyclopropanes
DNA Bacterial Serum Operon Mutant Virulence Microbiology fatty acids Enterococcus faecalis Gene Expression Regulation Enzymologic 03 medical and health sciences chemistry.chemical_compound Mice Bacterial Proteins cyclopropane ring formation [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Animals Humans Molecular Biology Fatty acid synthesis 030304 developmental biology antibiotic target 2. Zero hunger chemistry.chemical_classification 0303 health sciences Mice Inbred BALB C biology 030306 microbiology Fatty acid Gene Expression Regulation Bacterial Methyltransferases biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology 3. Good health Culture Media Enzyme chemistry [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases septicemic infection FASII pathway Female [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Bacteria Research Article |
| Zdroj: | Journal of Bacteriology Journal of Bacteriology, 2021, 203 (20), pp.e0022121. ⟨10.1128/JB.00221-21⟩ J Bacteriol Journal of Bacteriology, American Society for Microbiology, 2021, 203 (20), pp.e0022121. ⟨10.1128/JB.00221-21⟩ |
| ISSN: | 0021-9193 1098-5530 |
| DOI: | 10.1128/JB.00221-21⟩ |
| Popis: | Enterococcus faecalis, a multiple antibiotic-resistant Gram-positive bacterium, has emerged as a serious nosocomial pathogen. Here, we used a genetic approach to characterize the strategies used by E. faecalis to fulfill its requirements for endogenous fatty acid (FA) synthesis in vitro and in vivo. The type II fatty acid synthesis (FASII) pathway is encoded by two operons and two monocistronic genes. Expression of all of these genes is repressed by exogenous FAs, which are incorporated into the E. faecalis membrane and modify its composition. Deletion of nine genes of the 12-gene operon abolished growth in an FA-free medium. Addition of serum, which is lipid rich, restored growth. Interestingly, the E. faecalis membrane contains cyclic fatty acids that modify membrane properties but that are unavailable in host serum. The cfa gene that encodes the cyclopropanation process is located in a locus independent of the FASII genes. Its deletion did not alter growth under the conditions tested, but yielded bacteria devoid of cyclic FAs. No differences were observed between mice infected with wild-type (WT) or with FASII or cyclopropanation mutant strains, in terms of bacterial loads in blood, liver, spleen, or kidneys. We conclude that in E. faecalis, neither FASII nor cyclopropanation enzymes are suitable antibiotic targets. IMPORTANCE Membrane lipid homeostasis is crucial for bacterial physiology, adaptation, and virulence. Fatty acids are constituents of the phospholipids that are essential membrane components. Most bacteria incorporate exogenous fatty acids into their membranes. Enterococcus faecalis has emerged as a serious nosocomial pathogen that is responsible for urinary tract infections, bacteremia, and endocarditis and is intrinsically resistant to numerous antibiotics. E. faecalis synthesizes saturated and unsaturated fatty acids, as well as cyclic fatty acids that are not found in the human host. Here, we characterized mutant strains deficient in fatty acid synthesis and modification using genetic, biochemical, and in vivo approaches. We conclude that neither the fatty acid synthesis pathway nor the cyclopropanation enzyme are suitable targets for E. faecalis antibiotic development. |
| Databáze: | OpenAIRE |
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