Format

Send to

Choose Destination
J Med Microbiol. 2002 Jan;51(1):34-41.

Linkage between toxin production and purine biosynthesis in Clostridium difficile.

Author information

1
Department of Bacteriology, School of Medicine, Kanazawa University, Japan.

Abstract

The production of toxins A and B by Clostridium difficile was greatly enhanced under biotin-limited conditions, in which a 140-kDa protein was expressed strongly. Gene cloning revealed that this protein was a homologue of formylglycinamidine ribonucleotide synthetase (FGAM synthetase, EC 6.3.5.3), which is known as PurL in Escherichia coli and catalyses the fourth step of the de novo purine biosynthesis pathway. This enzyme consisted of a single polypeptide, although FGAM synthetases of gram-positive bacteria usually consist of two subunits. Inhibition of the enzymic activity of C. difficile PurL by O-diazoacetyl-L-serine (azaserine) resulted in enhanced toxin B production even in biotin-sufficient conditions. In contrast, blockade of the preceding step of the PurL catalysing step by sulfamethoxazole inhibited toxin B production almost completely. These results suggest that accumulation of formylglycinamide ribonucleotide (FGAR), a substrate of FGAM synthetase, enhances toxin production by C difficile and depletion of FGAR reduces toxin production.

PMID:
11800470
DOI:
10.1099/0022-1317-51-1-34
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Ingenta plc
Loading ...
Support Center