Pyrrolnitrin from Burkholderia cepacia: antibiotic activity against fungi and novel activities against streptomycetes

Abstract

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.

Burkholderia phytofirmans sp. nov., a novel plant-associated bacterium with plant-beneficial properties

“…Burkholderia cepacia, the type species of the genus, was initially described as the causative agent of onion soft rot (Burkholder, 1950), but many strains belonging to the B. cepacia complex are also able to promote plant health (Parke & Gurian-Sherman, 2001). Similarly, other Burkholderia species have been reported to exhibit plant-growth-promoting or biocontrol effects (El Banna & Winkelmann, 1998;Tran Van et al, 2000;Estrada de los Santos et al, 2001). …”

Burkholderia cepacia aisladas de variedades de ñame con actividad antimicrobiana contra Colletotrichum gloeosporioides

“…Para el caso de B. cepacia, ha sido considerada una bacteria con un potencial para el control biológico de hongos fitopatógenos (JAYASWAL et al, 1990). La actividad inhibitoria de esta bacteria contra una diversidad de fitopatógenos ha sido atribuida a la producción de metabolitos secundarios como cepacina, pirrolnitrina, altericidina y otros compuestos volátiles y no volátiles aun no identificados (EL-BANNA y WINKELMANN, 1998;QUAN et al, 2006).…”

Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins

“…Studies on the mechanism of action of pyrrolnitrin showed that it probably blocks electron transfer between the dehydrogenases and the cytochrome components of the respiratory chain [29]. The introduction in the pentabromopseudilin of a carbonyl group between the phenyl group and the pyrrole moiety, i.e., compound 4 (Figure 1), entails an increase in antibacterial activity against Escherichia coli and Bacillus subtilis, whereas N-methylation is disadvantageous for the antibacterial activity [19,21].…”

“…Studies on the mechanism of action of pyrrolnitrin showed that it probably blocks electron transfer between the dehydrogenases and the cytochrome components of the respiratory chain [29]. …”

“…[24][25][26], Myxococcus fulvus [27], and Enterobacter agglomerans [28]. It shows antibacterial activity against Gram-positive pathogens, in particular against certain Streptomyces species, such as S. antibioticus and S. violaceoruber (MIC = 0.89 µM), against fungal strains, such as Paecilomyces variotii and Penicillium puberulum (MIC in the range 8.9-26.9 µM) [29], and against a range of mycobacteria, including Mycobacterium tuberculosis (MIC in the range 17.9-35.9 µM) [30]. This compound was launched in 1966 as an antifungal OTC drug in Japan.…”