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The Campylobacter jejuni Response Regulator and Cyclic-Di-GMP Binding CbrR Is a Novel Regulator of Flagellar Motility

A leading cause of bacterial gastroenteritis, Campylobacter jejuni is also associated with broad sequelae, including extragastrointestinal conditions such as reactive arthritis and Guillain-Barré Syndrome (GBS). CbrR is a C. jejuni response regulator that is annotated as a diguanylate cyclase (DGC),...

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Detalles Bibliográficos
Autores principales: Cox, Claudia A., Bogacz, Marek, El Abbar, Faiha M., Browning, Darren D., Hsueh, Brian Y., Waters, Chris M., Lee, Vincent T., Thompson, Stuart A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779298/
https://www.ncbi.nlm.nih.gov/pubmed/35056537
http://dx.doi.org/10.3390/microorganisms10010086
Descripción
Sumario:A leading cause of bacterial gastroenteritis, Campylobacter jejuni is also associated with broad sequelae, including extragastrointestinal conditions such as reactive arthritis and Guillain-Barré Syndrome (GBS). CbrR is a C. jejuni response regulator that is annotated as a diguanylate cyclase (DGC), an enzyme that catalyzes the synthesis of c-di-GMP, a universal bacterial second messenger, from GTP. In C. jejuni DRH212, we constructed an unmarked deletion mutant, cbrR(−), and complemented mutant, cbrR(+). Motility assays indicated a hyper-motile phenotype associated with cbrR(−), whereas motility was deficient in cbrR(+). The overexpression of CbrR in cbrR(+) was accompanied by a reduction in expression of FlaA, the major flagellin. Biofilm assays and scanning electron microscopy demonstrated similarities between DRH212 and cbrR(−); however, cbrR(+) was unable to form significant biofilms. Transmission electron microscopy showed similar cell morphology between the three strains; however, cbrR(+) cells lacked flagella. Differential radial capillary action of ligand assays (DRaCALA) showed that CbrR binds GTP and c-di-GMP. Liquid chromatography tandem mass spectrometry detected low levels of c-di-GMP in C. jejuni and in E. coli expressing CbrR. CbrR is therefore a negative regulator of FlaA expression and motility, a critical virulence factor in C. jejuni pathogenesis.