Proteomics

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The role of the Ser/Thr kinase PrkC of Clostridium difficile in cell wall homeostasis and antimicrobial resistance.


ABSTRACT: Clostridium difficile is the leading cause of antibiotic associated diarrhea in adults. During infection, the bacteria must rapidly respond and adapt to the host environment by being able to activate survival strategies. Ser/Thr kinases (STKs) are involved in signal transduction and regulate numerous physiological processes. PrkC of C. difficile is STK with two PASTA domains. We showed that this protein was membrane associated and localized at the septum. We observed that prkC deletion affects the cell morphology with an increased mean size, heterogeneity in length and the presence of abnormal septa. A ∆prkC mutant was able to sporulate and germinate but had a reduced motility and formed more biofilms than the wild-type strain. Moreover, a ∆prkC mutant showed an increased sensitivity to antimicrobial compounds targeting the envelope such as deoxycholate, a secondary bile salt, cephalosporins acting on peptidoglycan synthesis, cationic antimicrobial peptides and lysozyme. This increased susceptibility was not associated to differences in the structure of peptidoglycan or of polysaccharide II (PSII). A proteomic study showed that the majority of C. difficile proteins associated to the cell wall are less abundant in the ∆prkC mutant compared to the WT strain. Finally, the ∆prkC mutant presented a delay in gut establishment in a hamster model of infection while its virulence was not significantly affected.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Clostridioides Difficile

TISSUE(S): Culture Condition:anaerobically-grown Cell, Prokaryotic Cell

SUBMITTER: Thibaut Douché  

LAB HEAD: Bruno Dupuy

PROVIDER: PXD012241 | Pride | 2019-06-14

REPOSITORIES: Pride

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<i>Clostridium difficile</i> is the leading cause of antibiotic-associated diarrhea in adults. During infection, <i>C. difficile</i> 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 <i>C. difficile</i> is an STK with two PASTA domains. We showed that PrkC is membrane associated and is found at the septum. We o  ...[more]

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