Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trospectomycin sulfate (trospectomycin, TRS) is a novel, broad-spectrum, aminocyclitol antibiotic that is being developed clinically for the treatment of upper respiratory tract infections, bacterial vaginosis, pelvic inflammatory disease, and gonorrhea. This study investigated the bactericidal activity (by time-kill kinetics) and the postantibiotic effect (PAE) of TRS. Species-dependent bacteriostatic/bactericidal activity was observed for TRS; the antibiotic was bacteriostatic for Staphylococcus epidermidis, Enterococcus faecalis, and Escherichia coli, and bactericidal for Haemophilus influenzae, Neisseria gonorrhoeae, Moraxella catarrhalis, and Bacteroides fragilis (one of two test strains). When TRS was tested at four times its minimum inhibitory concentration or at a maximum test concentration of 32 micrograms/ml, with a 1-hr exposure period, the following PAE values were recorded: S. epidermidis 30032, 1.8 hr, En. faecalis ATCC 29212, 1.6 hr, E. coli UC 311, 1.5 hr, E. coli UC 9451, 1.5 hr, H. influenzae 30063, greater than 4.0 hr, B. fragilis ATCC 25285, 5.2 hr, and B. fragilis UC 12199, 6.7 hr. The broad-spectrum PAE that was observed for TRS is somewhat unique compared with other antibiotics.
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PMID:The bactericidal activity and postantibiotic effect of trospectomycin. 138 66

A gene essential for the development of genetic competence in Haemophilus influenzae (Hi) was identified as a homolog of the Escherichia coli (Ec) topA gene, which encodes DNA topoisomerase I (TopI). The Hi topA locus was initially identified by mini-Tn10kan mutagenesis. Three independent insertion events within 500 bp of each other resulted in mutant strains that shared a similar phenotype. Each was deficient in competence-induced DNA binding, showed increased sensitivity to UV irradiation, and had an increased doubling time as compared to the wild-type (wt) strain. The nucleotide sequence of a 6.6-kb fragment containing the wt allele was determined. The sequence contained an open reading frame (ORF) of 868 amino acids (aa) that was interrupted by each of the mini-Tn10kan mutations. The deduced aa sequence had a molecular mass of 98 155 Da, a pI of 8.59 and showed strong similarity to Ec TopI. Examination of the topoisomer distribution of a test plasmid in an Hi mutant carrying an insertion in this ORF showed an increase in the level of supercoiling, indicating that TopI is necessary to relax supercoiled DNA in Hi. Complementation studies and insertional inactivation of genes downstream from topA indicated that TopI and not some downstream gene product was essential for competence. Four other ORFs were identified and two of these had homology to known genes. ORF1, which was truncated at one end of the sequenced region, shared strong sequence similarity to the C-terminal end of Ec pyridine nucleotide transhydrogenase beta subunit. ORF4, which was also truncated, showed strong sequence similarity to the N-terminal end of the Ec threonyl-tRNA synthetase.
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PMID:Characterization of the Haemophilus influenzae topA locus: DNA topoisomerase I is required for genetic competence. 863 45

A series of potent and bacteria-selective threonyl-tRNA synthetase (ThrRS) inhibitors have been identified using structure-based drug design. These compounds occupied the substrate binding site of ThrRS and showed excellent binding affinities for all of the bacterial orthologues tested. Some of the compounds displayed greatly improved bacterial selectivity. Key residues responsible for potency and bacteria/human ThrRS selectivity have been identified. Antimicrobial activity has been achieved against wild-type Haemophilus influenzae and efflux-deficient mutants of Escherichia coli and Burkholderia thailandensis.
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PMID:Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design. 2336 38