Repression of Clostridium difficile toxin gene expression by CodY

被引:181
作者
Dineen, Sean S.
Villapakkam, Anuradha C.
Nordman, Jared T.
Sonenshein, Abraham L. [1 ]
机构
[1] Tufts Univ, Dept Mol Biol & Microbiol, Sch Med, Boston, MA 02111 USA
[2] Tufts Univ, Sackler Sch Grad Biomed Sci, Program Mol Microbiol, Boston, MA 02111 USA
关键词
D O I
10.1111/j.1365-2958.2007.05906.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CodY, a global regulator of gene expression in low G + C Gram-positive bacteria, was found to repress toxin gene expression in Clostridium difficile. Inactivation of the codYgene resulted in derepression of all five genes of the C. difficile pathogenicity locus during exponential growth and stationary phase. CodY was found to bind with high affinity to a DNA fragment containing the promoter region of the tcdR gene, which encodes a sigma factor that permits RNA polymerase to recognize promoters of the two major toxin genes as well as its own promoter. CodY also bound, but with low affinity, to the toxin gene promoters, suggesting that the regulation of toxin gene expression by CodY occurs primarily through direct control of tcdR gene expression. Binding of CodY to the tcdR promoter region was enhanced in the presence of GTP and branched-chain amino acids, suggesting a link between nutrient limitation and the expression of C. difficile toxin genes.
引用
收藏
页码:206 / 219
页数:14
相关论文
共 53 条
[51]   TRANSFERABLE RESISTANCE TO CLINDAMYCIN, ERYTHROMYCIN, AND TETRACYCLINE IN CLOSTRIDIUM-DIFFICILE [J].
WUST, J ;
HARDEGGER, U .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1983, 23 (05) :784-786
[52]   TOXIN PRODUCTION BY CLOSTRIDIUM-DIFFICILE IN A DEFINED MEDIUM WITH LIMITED AMINO-ACIDS [J].
YAMAKAWA, K ;
KAMIYA, S ;
MENG, XQ ;
KARASAWA, T ;
NAKAMURA, S .
JOURNAL OF MEDICAL MICROBIOLOGY, 1994, 41 (05) :319-323
[53]   Inhibition of enhanced toxin production by Clostridium difficile in biotin-limited conditions [J].
Yamakawa, K ;
Karasawa, T ;
Ohta, T ;
Hayashi, H ;
Nakamura, S .
JOURNAL OF MEDICAL MICROBIOLOGY, 1998, 47 (09) :767-771