title: Spirotetronate antibiotics with anti-Clostridium activity from Actinomadura sp. 2EPS.
abstract: The rare actinomycetes strain 2EPS was isolated from soil and analysis of cultural, morphological characteristics, diaminopimelic acid content of its cell wall, and 16S rRNA gene sequence indicates that 2EPS belongs to genus Actinomadura. In addition, neighbor-joining phylogenetic tree also confirmed the relationships of this strain to other members of Actinomadura. A butanol extract with antibacterial activity was purified by reversed-phase chromatography to obtain three bioactive compounds, designated as compounds 1, 2 and 3. The structures of these compounds were determined using spectroscopic analysis ((1)H-NMR and (13)C-NMR) and mass spectrometric analysis (HR-TOF-MS). Compounds 1-3 were identified and found to be the same as those included in the Japanese patent number JP 09227587 for spirotetronate antibiotics and are BE-45722A (1), BE-45722B (2) and BE-45722C (3), respectively. All compounds were active against Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 14579, and B. subtilis ATCC 6633) with low MIC values between 0.08 and 5.0 µg/ml. Moreover, both 1 and 3 also exhibited strong activity, with similar MIC values, against Clostridium perfringens S107 at 0.63 µg/ml and C. difficile 630 at 0.08 µg/ml. These results suggest the identified spirotetronate compounds may have potential in the treatment of Clostridium infections. Overall, this analysis demonstrates that rare actinomycetes are a promising source for discovery of antimicrobial compounds.
authors.affiliation: Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Jirayut
authors.initials: J
authors.lastname: Euanorasetr
authors.forename: Bungonsiri
authors.initials: B
authors.lastname: Intra
authors.forename: Phayungsak
authors.initials: P
authors.lastname: Mongkol
authors.forename: Surang
authors.initials: S
authors.lastname: Chankhamhaengdecha
authors.forename: Patoomratana
authors.initials: P
authors.lastname: Tuchinda
authors.forename: Mihoko
authors.initials: M
authors.lastname: Mori
authors.forename: Kazuro
authors.initials: K
authors.lastname: Shiomi
authors.forename: Takuya
authors.initials: T
authors.lastname: Nihira
authors.forename: Watanalai
authors.initials: W
authors.lastname: Panbangred
mesh_terms: D000192:Actinomycetales / Q000737:chemistry* / Q000145:classification / Q000302:isolation & purification*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000440:Butanols / Q000737:chemistry / Q000494:pharmacology*; D056148:Chromatography, Reverse-Phase; D003013:Clostridium / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012988:Soil Microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000440:Butanols; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S