Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034186 (pyelonephritis)
 6,144 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasmid-encoded fimbriae (Pef) expressed by Salmonella typhimurium mediate adhesion to mouse intestinal epithelium. The pef operon shares features with the Escherichia coli pyelonephritis-associated pilus (pap) operon, which is under methylation-dependent transcriptional regulation. These features include conserved DNA GATC box sites in the upstream regulatory region as well as homologues of the PapI and PapB regulatory proteins. Unlike Pap fimbriae, which are expressed in a variety of laboratory media, Pef fimbriae were expressed only in acidic, rich broth under standing culture conditions. Analysis of S. typhimurium grown under these conditions indicated that Pef production was regulated by a phase variation mechanism, in which the bacterial population was skewed between fimbrial expression (phase ON) and non-expression (phase OFF) states. Leucine-responsive regulatory protein (Lrp) and DNA adenine methylase (Dam) were required for pef transcription. In contrast, the histone-like protein (H-NS) and the stationary-phase sigma factor (RpoS) repressed pef transcription. Methylation of the pef GATC II site appeared to be required for pef fimbrial expression based on analysis of a GCTC II mutant that did not express Pef fimbriae. Analysis of the DNA methylation states of pef GATC sites indicated that, under acidic growth conditions, which induced Pef production, most GATC I sites were non-methylated, whereas GATC II and GATC X were predominantly methylated. The methylation protection at GATC I and GATC II was dependent upon Lrp and was modulated by PefI. Together, these results indicate that Pef production is regulated by DNA methylation, which is the first example of methylation-dependent gene regulation outside of E. coli.
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PMID:DNA methylation-dependent regulation of pef expression in Salmonella typhimurium. 1069 51

A comparative study was completed to determine the influence of various environmental stimuli on the transcription of three different fimbrial operons in Escherichia coli and to determine the role of the histone-like protein H-NS in this environmental regulation. The fimbrial operons studied included the pap operon, which encodes pyelonephritis-associated pili (P pili), the daa operon, which encodes F1845 fimbriae, and the fan operon, which encodes K99 fimbriae. Using lacZYA transcriptional fusions within each of the fimbrial operons, we tested temperature, osmolarity, carbon source, rich medium, oxygen levels, pH, amino acids, solid medium, and iron concentration for their effects on fimbrial gene expression. Low temperature, high osmolarity, glucose as a carbon source, and rich medium repressed transcription of all three operons. High iron did not alter transcription of any of the operons tested, whereas the remaining stimuli had effects on individual operons. For the pap and daa operons, introduction of the hns651 mutation relieved the repression, either fully or partially, due to low temperature, glucose as a carbon source, rich medium, and high osmolarity. Taken together, these data indicate that there are common environmental cues that regulate fimbrial transcription in E. coli and that H-NS is an important environmental regulator for fimbrial transcription in response to several stimuli.
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PMID:H-NS controls pap and daa fimbrial transcription in Escherichia coli in response to multiple environmental cues. 1105 83

Epigenetics is the study of heritable changes in DNA or its associated proteins except mutations in gene sequence. Epigenetic regulation plays fundamental roles in the processes of kidney cell biology through the action of DNA methylation, chromatin modifications via epigenetic regulators and interaction via transcription factors, and noncoding RNA species. Kidney diseases, including acute kidney injury, chronic kidney disease, nephritic and nephrotic syndromes, pyelonephritis and polycystic kidney diseases are driven by aberrant activity in numerous signaling pathways in even individual kidney cell. Epigenetic alterations, including DNA methylation, histone acetylation and methylation, noncoding RNAs, and protein posttranslational modifications, could disrupt essential pathways that protect the renal cells from uncontrolled growth, apoptosis and establishment of other renal associated syndromes, which have been recognized as one of the critical mechanisms for regulating functional changes that drive and maintain the kidney disease phenotype. In this chapter, we briefly summarize the epigenetic mechanisms in kidney cell biology and epigenetic basis of kidney development, and introduce epigenetic techniques that can be used in investigating the molecular mechanism of kidney cell biology and kidneys diseases, primarily focusing on the integration of DNA methylation and chromatin immunoprecipitation technologies into kidney disease associated studies. Future studies using these emerging technologies will elucidate how alterations in the renal cell epigenome cooperate with genetic aberrations for kidney disease initiation and progression. Incorporating epigenomic testing into the clinical research is essential to future studies with epigenetics biomarkers and precision medicine using emerging epigenetic therapies.
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PMID:Investigation of epigenetics in kidney cell biology. 3139 83