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The structure of the cofactor binding GAF domain of the nutrient sensor CodY from Clostridium difficileThe structure of the cofactor binding GAF domain of the nutrient sensor CodY from Clostridium difficile
Structural highlights
FunctionQ18BE1_CLOD6 DNA-binding global transcriptional regulator which is involved in the adaptive response to starvation and acts by directly or indirectly controlling the expression of numerous genes in response to nutrient availability. During rapid exponential growth, CodY is highly active and represses genes whose products allow adaptation to nutrient depletion.[HAMAP-Rule:MF_00621] Publication Abstract from PubMedToxin synthesis and endospore formation are two of the most critical factors that determine the outcome of infection by Clostridioides difficile. The two major toxins, TcdA and TcdB, are the principal factors causing damage to the host. Spores are the infectious form of C. difficile, permit survival of the bacterium during antibiotic treatment and are the predominant cell form that leads to recurrent infection. Toxin production and sporulation have their own specific mechanisms of regulation, but they share negative regulation by the global regulatory protein CodY. Determining the extent of such regulation and its detailed mechanism is important for understanding the linkage between two apparently independent biological phenomena and raises the possibility of creating new ways of limiting infection. The work described here shows that a codY null mutant of a hypervirulent (ribotype 027) strain is even more virulent than its parent in a mouse model of infection and that the mutant expresses most sporulation genes prematurely during exponential growth phase. Moreover, examining the expression patterns of mutants producing CodY proteins with different levels of residual activity revealed that expression of the toxin genes is dependent on total CodY inactivation, whereas most sporulation genes are turned on when CodY activity is only partially diminished. These results suggest that, in wild-type cells undergoing nutrient limitation, sporulation genes can be turned on before the toxin genes. Impact of CodY protein on metabolism, sporulation and virulence in Clostridioides difficile ribotype 027.,Daou N, Wang Y, Levdikov VM, Nandakumar M, Livny J, Bouillaut L, Blagova E, Zhang K, Belitsky BR, Rhee K, Wilkinson AJ, Sun X, Sonenshein AL PLoS One. 2019 Jan 30;14(1):e0206896. doi: 10.1371/journal.pone.0206896., eCollection 2019. PMID:30699117[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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