The Ser/Thr kinase PrkC participates in cell wall homeostasis and antimicrobial resistance in Clostridium difficile
| Autor: | Bruno Dupuy, Thomas Candela, Sandrine Denis-Quanquin, Transito Garcia-Garcia, Elodie Cuenot, Marie-Pierre Chapot-Chartier, Olivier Gorgette, Mariette Matondo, Claire Janoir, Yannick D. N. Tremblay, Thibaut Douché, Pascal Courtin, Sandra Hoys, Isabelle Martin-Verstraete |
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| Přispěvatelé: | Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris] (IP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Laboratoire de Chimie - UMR5182 (LC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bactéries, Pathogènes et Santé (UBaPS), Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11), This work was funded by the Institut Pasteur, the University Paris 7, the ITN Marie Curie, Clospore (H2020-MSCA-ITN-7082014 642068) and the ANR DifKin (ANR-17-CE15-0018-01). EC and TGG are the recipient of a ITN Marie Curie and an ANR fellowships, respectively., ANR-17-CE15-0018,DifKin,Une Ser/Thr kinase impliquée dans la résistance à des composés antimicrobiens importants pour la colonization chez Clostridium difficile(2017), European Project: 642068,H2020,H2020-MSCA-ITN-2014,CLOSPORE(2015), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], Technologie et Service BioImagerie Ultrastructurale – Ultrastructural BioImaging (UTechS UBI), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Université Paris-Saclay, Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
envelope homeostasis
Immunology Mutant Cell Virulence Microbial Sensitivity Tests Peptidoglycan Biology Protein Serine-Threonine Kinases Cell morphology Microbiology Cell wall 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Cell Wall CAMPs Cricetinae Hanks kinase Drug Resistance Bacterial medicine Animals Homeostasis cephalosporin sensitivity 030304 developmental biology cell morphology 0303 health sciences Mesocricetus 030306 microbiology Clostridioides difficile Bacterial Infections Clostridium difficile Infectious Diseases medicine.anatomical_structure [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology chemistry Parasitology Cell envelope biofilms |
| Zdroj: | Infection and Immunity Infection and Immunity, 2019, 87 (8), pp.e00005-19. ⟨10.1128/IAI.00005-19⟩ Infection and Immunity, American Society for Microbiology, 2019, ⟨10.1128/IAI.00005-19⟩ Infection and Immunity, American Society for Microbiology, 2019, 87 (8), pp.e00005-19. ⟨10.1128/IAI.00005-19⟩ |
| ISSN: | 0019-9567 1098-5522 |
| Popis: | International audience; Clostridium difficile is the leading cause of antibiotic-associated diarrhea in adults. During infection, C. difficile must detect the host environment and induce an appropriate survival strategy. Signal transduction networks involving serine/threonine kinases (STKs) play key roles in adaptation, as they regulate numerous physiological processes. PrkC of C. difficile is a STK with two PASTA domains. We showed that PrkC is membrane associated and is found at the septum. We observed that deletion of prkC affects cell morphology with an increase in mean size, cell length heterogeneity, and presence of abnormal septa. When compared with the wild-type strain, a ΔprkC mutant was able to sporulate and germinate but was less motile and formed more biofilm. Moreover, a ΔprkC mutant was more sensitive to antimicrobial compounds that target the cell envelope such as the secondary bile salt deoxycholate, cephalosporins, cationic antimicrobial peptides, and lysozyme. This increased susceptibility was not associated with differences in peptidoglycan or polysaccharide II composition. However, the ΔprkC mutant had less peptidoglycan and released more polysaccharide II into the supernatant. A proteomic analysis showed that the majority of C. difficile proteins associated with the cell wall were less abundant in the ΔprkC mutant compared to the wild-type strain. Finally, in a hamster model of infection the ΔprkC mutant had a colonization delay that did not significantly affect overall virulence. |
| Databáze: | OpenAIRE |
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