Linkage between toxin production and purine biosynthesis in Clostridium difficile.
J Med Microbiol
; 51(1): 34-41, 2002 Jan.
Article
em En
| MEDLINE
| ID: mdl-11800470
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Purinas
/
Toxinas Bacterianas
/
Biotina
/
Clostridioides difficile
/
Proteínas de Escherichia coli
/
Enterotoxinas
/
Glicina
/
Ligases
Limite:
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article