Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mutant AIR38 is isolated from Escherichia coli K-12 strain deficient in thymidilate synthetase and deoxyriboaldolase (HfrH, thy, dra)--by selection for low thymine requirement on the medium containing inosine as the carbon source. Under the conditions mentioned the mutant AIR38 (thy, dra) grows at low thymine concentration (2 mkg/ml), and is uncapable to grow in the presence of thymidine (40 mkg/ml). Dra+ derivatives of the AIR38 do no catabolize inozine in the presence of thymidine as well. The mutation AIR38 is mapped within the deo-operon between drm and pup mutation markers. The levels of phosphodeoxyribomutase and purine nucleoside phosphorylase in cell extracts of AIR38 are 2.5-6-fold decreased. In transductional experiments with phage P1 and the mutant AIR38 as recipient the delayed haploidization of merozygotes dra+, AIR+/dra, AIR38, thy and the dominant expression of the sensitivity to thymidine in the presence of inosine as the carbon source are observed. It is supposed that the mutation AIR38 affects the structural gene of purine nucleoside phosphorilase by altering the mode of interaction of this enzyme with the membrane under the conditions of thymine starvation.
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PMID:[Regulation of the activity of Escherichia coli deo-operon structural genes: the mutation mapped within the operon boundaries and affecting drm and pup gene activity]. 36 45

The phagosomal transporter (Pht) family of the major facilitator superfamily (MFS) is encoded by phylogenetically related intracellular gammaproteobacteria, including the opportunistic pathogen Legionella pneumophila. The location of the pht genes between the putative thymidine kinase (tdk) and phosphopentomutase (deoB) genes suggested that the phtC and phtD loci contribute to thymidine salvage in L. pneumophila. Indeed, a phtC(+) allele in trans restored pyrimidine uptake to an Escherichia coli mutant that lacked all known nucleoside transporters, whereas a phtD(+) allele did not. The results of phenotypic analyses of L. pneumophila strains lacking phtC or phtD strongly indicate that L. pneumophila requires PhtC and PhtD function under conditions where sustained dTMP synthesis is compromised. First, in broth cultures that mimicked thymidine limitation or starvation, L. pneumophila exhibited a marked requirement for PhtC function. Conversely, mutation of phtD conferred a survival advantage. Second, in medium that lacked thymidine, multicopy phtC(+) or phtD(+) alleles enhanced the survival of L. pneumophila thymidylate synthase (thyA)-deficient strains, which cannot synthesize dTMP endogenously. Third, under conditions in which transport of the pyrimidine nucleoside analog 5-fluorodeoxyuridine (FUdR) would inhibit growth, PhtC and PhtD conferred a growth advantage to L. pneumophila thyA(+) strains. Finally, when cultured in macrophages, L. pneumophila required the phtC-phtD locus to replicate. Accordingly, we propose that PhtC and PhtD contribute to protect L. pneumophila from dTMP starvation during its intracellular life cycle.
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PMID:The phtC-phtD locus equips Legionella pneumophila for thymidine salvage and replication in macrophages. 2447 86