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Impact of CodY protein on metabolism, sporulation and virulence in Clostridioides difficile ribotype 027
DOI:
10.1371/journal.pone.0206896
Authors:
Nadine
Daou
(Tufts University School of Medicine)
,
Yuanguo
Wang
(Tufts University)
,
Vladimir M.
Levdikov
(University of York)
,
Madhumitha
Nandakumar
(Weill Cornell Medical College)
,
Jonathan
Livny
(Broad Institute of MIT and Harvard)
,
Laurent
Bouillaut
(Tufts University School of Medicine)
,
Elena
Blagova
(University of York)
,
Keshan
Zhang
(Tufts University)
,
Boris R.
Belitsky
(Tufts University School of Medicine)
,
Kyu
Rhee
(Weill Cornell Medical College)
,
Anthony J.
Wilkinson
(University of York)
,
Xingmin
Sun
(University of South Florida)
,
Abraham L.
Sonenshein
(Tufts University School of Medicine)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Plos One
, VOL 14
State:
Published (Approved)
Published:
January 2019
Diamond Proposal Number(s):
9948

Abstract: Toxin 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.
Journal Keywords: Clostridium difficile; Toxins; Bacterial sporulation; Gene regulation; Mutant strains; Gene expression; Bacterial spores; Operons
Diamond Keywords: Bacteria
Subject Areas:
Biology and Bio-materials
Instruments:
I02-Macromolecular Crystallography
Added On:
02/05/2019 09:57
Documents:
bhhh55.pdf
Discipline Tags:
Pathogens
Infectious Diseases
Health & Wellbeing
Genetics
Structural biology
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)