Pyrrolnitrin from Burkholderia cepacia: antibiotic activity against fungi and novel activities against streptomycetes.
A bacterial strain identified as Burkholderia cepacia NB-1 was isolated from water ponds in the botanical garden in Tübingen, Germany, and was found to produce a broad spectrum phenylpyrrole antimicrobial substance active against filamentous fungi, yeasts and Gram-positive bacteria. In batch culture containing glycerol and L-glutamic acid, the isolate NB-1 produced the antibiotic optimally late in the growth phase and accumulated a main portion in their cells. Isolation and purification of the antibiotic from Burkholderia (Pseudomonas) cepacia NB-1 by acetone extraction, gel filtration on Sephadex LH-20 and preparative HPLC yielded 0.54 mg l-1 of a pure substance. Spectroscopic data (HPLC, MS and NMR) confirmed that the compound was pyrrolnitrin [3-chloro-4-(2'-nitro-3'-chloro-phenyl) pyrrole]. Pyrrolnitrin has an inhibitory effect on the electron transport system, as demonstrated by isolated mitochondria from Neurospora crassa 74 A. This inhibition was relieved by N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD), indicating that pyrrolnitrin blocked the electron transfer between the dehydrogenases and the cytochrome components of the respiratory chain. Among Gram-positive bacteria, pyrrolnitrin was most active against certain Streptomyces species, especially S. antibioticus, which has not previously been described in the literature. In the presence of pyrrolnitrin, aerial mycelium and spore formation of Strep. antibioticus was suppressed, although growth continued via substrate mycelium. The new findings of inhibition of streptomycetes and their secondary metabolism by pyrrolnitrin may contribute to the fact that Pseudomonas species predominate in soil and compete even with antibiotic-producing Streptomyces.
el-Banna
N
N
University of Tübingen, Germany.
Winkelmann
G
G
D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016956:Burkholderia cepacia / Q000737:chemistry* / Q000145:classification / Q000254:growth & development; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D008928:Mitochondria / Q000378:metabolism; D009492:Neurospora crassa / Q000187:drug effects* / Q000378:metabolism; D011764:Pyrrolnitrin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013170:Spores / Q000187:drug effects; D013302:Streptomyces / Q000187:drug effects* / Q000502:physiology; D013772:Tetramethylphenylenediamine / Q000378:metabolism; D014871:Water Microbiology
D000935:Antifungal Agents; D011764:Pyrrolnitrin; D013772:Tetramethylphenylenediamine