Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Campylobacter jejuni is a leading cause of foodborne illness in industrialized countries. This pathogen exhibits significant strain-to-strain variability, which results in differences in virulence potential and clinical presentations. Here, we report that acquisition of the capacity to utilize specific nutrients enhanced the ability of a highly pathogenic strain of C. jejuni to colonize specific tissues. The acquisition of a gene encoding a gamma-glutamyltranspeptidase enabled this strain to utilize glutamine and glutathione and enhanced its ability to colonize the intestine. Furthermore, the acquisition of a DNA segment, which added a sec-dependent secretion signal to an otherwise cytoplasmic asparaginase, allowed this pathogen to utilize asparagine and to more efficiently colonize the liver. Our results reveal that subtle genetic changes in a bacterial pathogen result in significant changes in its ability to colonize specific tissues. In addition, these studies revealed remarkably specific nutritional requirements for a pathogen to effectively colonize different tissues.
 ...
PMID:Metabolic diversity in Campylobacter jejuni enhances specific tissue colonization. 1899 38

In addition to their classical roles as carbon or nitrogen sources, amino acids can be used for bacterial virulence, colonization, or stress resistance. We found that original deamidase-transport systems impact colonization by Helicobacter pylori, a human pathogen associated with gastric pathologies, including adenocarcinoma. We demonstrated that l-asparaginase (Hp-AnsB) and gamma-glutamyltranspeptidase (Hp-gammaGT) are highly active periplasmic deamidases in H. pylori, producing ammonia and aspartate or glutamate from asparagine and glutamine, respectively. Hp-GltS was identified as a sole and specialized transporter for glutamate, while aspartate was exclusively imported by Hp-DcuA. Uptake of Gln and Asn strictly relies on indirect pathways following prior periplasmic deamidation into Glu and Asp. Hence, in H. pylori, the coupled action of periplasmic deamidases with their respective transporters enables the acquisition of Glu and Asp from Gln and Asn, respectively. These systems were active at neutral rather than acidic pH, suggesting their function near the host epithelial cells. We showed that Hp-DcuA, the fourth component of these novel deamidase-transport systems, was as crucial as Hp-gammaGT, Hp-AnsB, and Hp-GltS for animal model colonization. In conclusion, the pH-regulated coupled amino acid deamidase-uptake system represents an original optimized system that is essential for in vivo colonization of the stomach environment by H. pylori. We propose a model in which these two nonredundant systems participate in H. pylori virulence by depleting gastric or immune cells from protective amino acids such as Gln and producing toxic ammonia close to the host cells.
 ...
PMID:Coupled amino acid deamidase-transport systems essential for Helicobacter pylori colonization. 2036 42