title: Isolation and characterization of Streptomyces sp KH-614 producing anti-VRE (vancomycin-resistant enterococci) antibiotics.
abstract: The actinomycete strain KH-614 was antagonistic to vancomycin-resistant enterococci (VRE). Based on the diaminopimelic acid (DAP) type, morphological and physiological characteristics examined by scanning electron microscopy (SEM), KH-614 was confirmed as belonging to the genus Streptomyces. Based on the 16S rDNA nucleotide sequences, Streptomyces sp. KH-614 was found to have a relationship with Streptomyces lydicus. The production of antibiotic from this strain was most favorable when cultured in glucose, polypeptone, yeast extract (PY) medium for 6 days at 27 degrees C. The antibiotic was identified as a cyclo(L-leucyl-L-prolyl) by comparing it with the reported spectral data including MS and NMR. Cyclo(leu-pro) was found to be active against twelve VRE strains, including E. faecium (vanA, vanB), and E. faecalis (vanA, vanB), that had been isolated over a period three years (1998-2000). Cyclo(leu-pro) was especially effective against VRE strains such as E. faecalis (K-99-34), E. faecalis (K-00-184), E. faecalis (K-00-221), and the MIC values were 12.5 microg/ml. Moreover, cyclo(leu-pro) was effective against three leukemic cell lines at concentrations below 100 microg/ml. At 100 mg/ml cyclo(leu-pro), K562, HL60, and U937 leukemic cell lines showed growth inhibition of 95, 91, and 93%, respectively. In a normal cell line, MDBK, cyclo(leu-pro) exerted 24% growth inhibition at a concentration of 100 microg/ml, and showed no inhibitory activity at concentrations below 10 microg/ml. These results indicate that cyclo(leu-pro) is a potential anti-leukemic and anti-VRE agent.
authors.affiliation: Department of Biological Science, Kongju National University, Kongju, 314-701, Korea.
authors.forename: Ki-Hyeong
authors.initials: KH
authors.lastname: Rhee
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D004275:DNA, Ribosomal / Q000032:analysis; D016983:Enterococcus / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects; D016984:Enterococcus faecium / Q000187:drug effects; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D004275:DNA, Ribosomal; D010456:Peptides, Cyclic; D012336:RNA, Ribosomal, 16S