Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0519030 (Klebsiella)
 21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Signal transduction by two-component regulatory systems involves phosphorylation of the receiver domain of a response regulator by the transmitter domain of the cognate histidine kinase. In the NtrBC system, phosphorylation of NtrC by NtrB results in transcriptional activation of nitrogen-regulated genes. We have used the yeast two-hybrid system to probe interactions between domains of the NtrB and NtrC proteins from Klebsiella pneumoniae. We constructed fusions from each of a series of proteins or protein domains to the activation and the DNA-binding domains of GAL4 and analysed expression of GAL1:lacZ and GAL1:HIS3 reporters in yeast. The DNA-binding domain of NtrC and the so-called sensor domain of NtrB appeared to provide the major determinants for dimerization of the fusion proteins. A strong and specific interaction was also shown between NtrB and NtrC, localized to the HN region of the NtrB transmitter module and to the NtrC receiver domain, whereas other domains of these proteins do not appear to contribute to the recognition specificity. The results presented here indicate that communication between two-component partners also involves protein-protein interactions that can be detected in vivo, suggesting that the yeast two-hybrid system is a powerful genetic tool for identifying functional partners of prokaryotic signal transduction pathways.
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PMID:Two-hybrid analysis of domain interactions involving NtrB and NtrC two-component regulators. 1129 84

ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter species) pathogens have characteristic multiple-drug resistance and cause an increasing number of nosocomial infections worldwide. Peptide-based therapeutics to treat ESKAPE infections might be an alternative to conventional antibiotics. Histatin 5 (Hst 5) is a salivary cationic histidine-rich peptide produced only in humans and higher primates. It has high antifungal activity against Candida albicans through an energy-dependent, non-lytic process; but its bactericidal effects are less known. We found Hst 5 has bactericidal activity against S. aureus (60-70% killing) and A. baumannii (85-90% killing) in 10 and 100 mM sodium phosphate buffer (NaPB), while killing of >99% of P. aeruginosa, 60-80% E. cloacae and 20-60% of E. faecium was found in 10 mM NaPB. Hst 5 killed 60% of biofilm cells of P. aeruginosa, but had reduced activity against biofilms of S. aureus and A. baumannii. Hst 5 killed 20% of K. pneumonia biofilm cells but not planktonic cells. Binding and uptake studies using FITC-labeled Hst 5 showed E. faecium and E. cloacae killing required Hst 5 internalization and was energy dependent, while bactericidal activity was rapid against P. aeruginosa and A. baumannii suggesting membrane disruption. Hst 5-mediated killing of S. aureus was both non-lytic and energy independent. Additionally, we found that spermidine conjugated Hst 5 (Hst5-Spd) had improved killing activity against E. faecium, E. cloacae, and A. baumannii. Hst 5 or its derivative has antibacterial activity against five out of six ESKAPE pathogens and may be an alternative treatment for these infections.
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PMID:Human Salivary Protein Histatin 5 Has Potent Bactericidal Activity against ESKAPE Pathogens. 2826 70