Chemical communication in proteobacteria: biochemical and structural studies of signal synthases and receptors required for intercellular signalling

Cell-cell communication via the production and detection of chemical signal molecules has been the focus of a great deal of research over the past decade. One class of chemical signals widely used by proteobacteria consists of N-acyl-homoserine lactones, which are synthesized by proteins related to LuxI of Vibrio fischeri and are detected by proteins related to the V. fischeri LuxR protein. A related marine bacterium, Vibrio harveyi, communicates using two chemical signals, one of which, autoinducer-2 (AI-2), is a furanone borate diester that is synthesized by the LuxS protein and detected by a periplasmic protein called LuxP. Evidence from a number of laboratories suggests that AI-2 may be used as a signal by diverse groups of bacteria, and might permit intergeneric signalling. These two families of signalling systems have been studied from the perspectives of physiology, ecology, biochemistry, and more recently, structural biology. Here, we review the biochemistry and structural biology of both acyl-homoserine-lactone-dependent and AI-2-dependent signalling systems.     

Three bourbonenolides and other sesquiterpene lactones from two vernonia species

A re-investigation of V. arkansana afforded several new sesquiterpene lactones, three bourbonenolides, obviously closely related to those isolated from this plant previously, a glaucolide and a methoxy derivative most probably formed by fragmentation of the corresponding bourbonenolide. From V. profuga in addition to known lactones a new guaianolide was isolated. The biogenetic relationships of the Vernonia sesquiterpene lactones are discussed briefly.     

Five mikanolide derivatives from mikania cynanchifolia and their biogenetic relationships

The investigation of the aerial parts of Mikania cynanchifolia afforded, in addition to miscandenin, five new sesquiterpene lactones, miscandenin-1,2-epoxide, an isomiscandenin and three further dilactones related to mikanolide. The structures of these new compounds were elucidated by high field ¹H NMR spectroscopy. The biogenetic relationships of the sesquiterpene lactones are briefly discussed.     

Genotoxicity of fungi evaluated by SOS microplate assay.

By an introduction of sodium dodecylsulfate for cell lysis and immunomicroplate for mass assay, the modified SOS microplate assay method was established and applied for the evaluation of genotoxicity of mycotoxins and fungal cultures. Among 20 mycotoxins, the carcinogenic dihydrobisfuranoids such as aflatoxin B1, sterigmatocystin, and versicolorin A were positive in the presence of the activation system. While, the carcinogenic anthraquinones and lactones such as luteoskyrin, rugulosin, ochratoxin A, patulin, and citrinin were negative. The survey on genotoxic fungi revealed that, among 15 fungal isolates Aspergillus versicolor, Emericella acristata, and others were positive. Additional survey on 265 fungal isolates have revealed that various Aspergillus genera such as A. flavus, A. parasiticus, A. ustus, A. nidulans, and others were positive for SOS induction, along with several isolates of Fusarium moniliforme. The chemical analysis revealed that the dihydrobisfuranoids such as aflatoxin B1, and sterigmatocystin were the major genotoxic metabolites of several Aspergillus species. The SOS microplate assay system is a simple and rapid procedure for the mass screening of genotoxic fungi, particularly of the dihydrobisfuranoids-producing strains.     

真菌苯二酚内酯聚酮类化合物生物合成研究进展

真菌苯二酚内酯类聚酮化合物具有抗癌和调节免疫系统等重要的生物活性,其生物合成是近年来的研究热点。介绍了苯二酚内酯的双聚酮合酶协作合成机制和组合生物合成,并以几种真菌苯二酚内酯生物合成途径为例,综述了相关的研究进展,以期为研究者提供参考。     

Mycotoxins as harmful indoor air contaminants

Fungal metabolites (mycotoxins) that pose a health hazard to humans and animals have long been known to be associated with mold-contaminated food and feed. In recent times, concerns have been raised about exposures to mycotoxin-producing fungi in indoor environments, e.g., damp homes and buildings. The principal mycotoxins that contaminate food and feed (alfatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone) are rarely if ever found in indoor environments, but their toxicological properties provide an insight into the difficulties of assessing the health effects of related mycotoxins produced by indoor molds. Although the Penicillium and Aspergillus genera of fungi are major contaminants of both food and feed products and damp buildings, the particular species and hence the array of mycotoxins are quite different in these environments. The mycotoxins of these indoor species and less common mycotoxins from Stachybotrys and Chaetomium fungi are discussed in terms of their health effects and the need for relevant biomarkers and long-term chronic exposure studies.     

向日葵对向日葵螟抗虫性的研究进展

向日葵螟是取食向日葵花盘及籽粒最为猖獗的一种害虫,可造成严重的产量损失。本文综述了向日葵对两种向日葵螟(欧洲葵螟Homoeosoma nebulellum Denis et Schiffermüller和美洲葵螟Homoeosoma electellum Hulst)抗虫性的研究进展,从向日葵的花药腺毛、瘦果性状、次生化合物(黑色素、倍半萜类化合物和花粉萃取物)等方面概括了向日葵和向日葵螟的互作关系,阐述了向日葵的形态结构及化学组成对向日葵螟抗虫性的作用,初步说明了向日葵对向日葵螟抗虫性的物理生化机制,并对未来在抗虫育种工作的启示及可能的应用进行了展望。     

Determination of mycotoxins in foods: current state of analytical methods and limitations

Mycotoxins are natural contaminants produced by a range of fungal species. Their common occurrence in food and feed poses a threat to the health of humans and animals. This threat is caused either by the direct contamination of agricultural commodities or by a “carry-over” of mycotoxins and their metabolites into animal tissues, milk, and eggs after feeding of contaminated hay or corn. As a consequence of their diverse chemical structures and varying physical properties, mycotoxins exhibit a wide range of biological effects. Individual mycotoxins can be genotoxic, mutagenic, carcinogenic, teratogenic, and oestrogenic. To protect consumer health and to reduce economic losses, surveillance and control of mycotoxins in food and feed has become a major objective for producers, regulatory authorities and researchers worldwide. However, the variety of chemical structures makes it impossible to use one single technique for mycotoxin analysis. Hence, a vast number of analytical methods has been developed and validated. The heterogeneity of food matrices combined with the demand for a fast, simultaneous and accurate determination of multiple mycotoxins creates enormous challenges for routine analysis. The most crucial issues will be discussed in this review. These are (1) the collection of representative samples, (2) the performance of classical and emerging analytical methods based on chromatographic or immunochemical techniques, (3) the validation of official methods for enforcement, and (4) the limitations and future prospects of the current methods.     

Mycotoxins in house dust problems and analytical Approaches

People in developed countries spend up to 90% of their time indoors. This led to an increased awareness for problems regarding indoor environment in the recent years. It is known that mycotoxins formed by moulds can be harmful to human health.The body burden of mycotoxins is caused primarily by the uptake of cereals and related products but sometimes also by animal products. However the health effects caused by indoor moulds are currently under investigation. Therefore the aim of an investigation program is to study mould-dependent health effects in a burdened population of the city of Leipzig, Germany. To estimate exposure situation house dust samples are collected from loaded apartments. To realise the measurements of selected mycotoxins in house dust the development of a suitable analytical method was necessary. Capillary electrophoresis in combination with a special clean up of the samples was found to be an useful tool for these investigations.     

应用生物法合成内酯化合物

内酯是广泛存在于自然界中具有生物活性的一类化合物。由于大多数内酯化合物具有手性,用化学方法合成不仅过程复杂,而且产率也不高。利用酶反应的特异性,应用生物法合成内酯化合物具有很好的应用前景,其中包括微生物次生代谢合成内酯,脂肪酸生物转化合成内酯和脂肪酶在有机相中催化羟基脂肪酸形成内酯。本文报道这些领域的进展。     

Sesquiterpene lactones inhibit inducible nitric oxide synthase gene expression in cultured rat aortic smooth muscle cells.

Nitric oxide (NO) is an important regulator and effector molecule in various inflammatory disease states. High output of NO during inflammation is generated by the inducible isoform of nitric oxide synthase (iNOS). Sesquiterpene lactones are derived from Mexican-Indian medicinal plants and are known to have potent anti-inflammatory properties. The mechanisms by which sesquiterpene lactones exert their anti-inflammatory effects are not fully understood. In the current studies we determined if the sesquiterpene lactones, parthenolide and isohelenin, modulate iNOS gene expression in cultured rat aortic smooth muscle cells (RASMC) treated with lipopolysaccharide and interferon-gamma. Treatment with parthenolide or isohelenin inhibited NO production and iNOS mRNA expression in a concentration-dependent manner. Transient transfection studies with an iNOS promoter-luciferase reporter plasmid demonstrated that parthenolide and isohelenin also inhibited activation of the iNOS promoter. Inhibition of iNOS promoter activation was associated with inhibition of both I-kappaBalpha degradation and nuclear translocation of NF-kappaB. Neither parthenolide nor isohelenin induced the heat shock response in RASMC. We conclude that sesquiterpene lactones inhibit iNOS gene expression by a mechanism involving stabilization of the I-kappaBalpha/NF-kappaB complex. This effect is not related to induction of the heat shock response. The ability of sesquiterpene lactones to inhibit iNOS gene expression may account, in part, for their anti-inflammatory effects.     

Pseudoguaianolides related to confertin from Stevia isomeca

The aerial parts of Stevia isomeca afforded, in addition to known compounds, four new sesquiterpene lactones, three pseudoguaianolides related to stevin and a xanthanolide. The structures were elucidated by spectroscopic methods and a few chemical transformations.     

Neue furanoeremophilane und weitere inhaltsstoffe aus südafrikanischen Senecio-arten

The investigation of further 27 South African and a few other Senecio species afforded in addition to known compounds 18 new furanoeremophilanes, most of them being cacalol derivatives, two new lactones, a new eudesmane derivative and four acyl pyrrole derivatives. The structures are elucidated by spectroscopic methods mainly. The chemical results on more than 140 species now available indicate much of chemotaxonomic interest. Together with the chemical data on related genera, the taxonomic situation of the subtribe Senecioninae is discussed in connection with the proposed new classification. The chemical data are in good agreement with this new arrangement.     

Allenic germacranolides,bourbonene derived lactones and other constituents from Vernonia species

An investigation of seven Vernonia species, mainly from northern Brazil, afforded in addition to known compounds three new unusual sesquiterpene lactones with an allenic group. Intensive NMR studies fully established the structures. Furthermore, two lactones derived from bourbonene, two new glaucolides, a new furansesquiterpene, a nerolidol derivative and two other sesquiterpenes derived from eudesmane were isolated. The biogenetic relationships of the sesquiterpene lactones present in Veronia species as well as the chemotaxonomic aspects are discussed.     

The fumigant and repellent activity of aliphatic lactones against Pediculus humanus capitis (Anoplura: Pediculidae)

New alternative insecticides are necessary for the chemical control of head lice. In this study the fumigant knockdown time 50% (KT50) and repellency index (RI) of three aliphatic lactones was compared with two essential oils and DDVP, against permethrin-resistance Pediculus humanus capitis from Argentina. In the fumigant assay, none of the lactones were effective compared to the highest activity of eucalyptus (KT50 15.53 m). In the repellency test, the three lactones were equally or more effective (RI ranging from 60.50 to 76.68) than the positive control (piperonal). These lactones are promising as head lice repellents.     

The role of "quorum sensing" regulation system in symbiotic interaction of bacteria Burkholderia cepacia and Pseudomonas aeruginosa during mixed infection

Data concerning mechanisms of strengthening virulence of bacteria B.cepacia and P.aeruginosa during experimental mixed-infection are submitted. Results of in vitro studies of acylhomoserine lactones (AHL) with various length of a carbon lateral circuit have shown that butanoyl-homoser-ine lactone (C4), hexanoyl-homoserine lactone (C6) and octanoyl-homoserine lactone (C8) separately and in various combinations display different effects on growth of bacteria, formation of colonies and production of pathogenicity factors. Experiments on animals have shown strengthening virulence of bacteria B.cepacia by C4, C6 and C8 lactones when introduced simultaneously. Strengthening of virulence of the P.aeruginosa strain under the action of lactone C6 and simultaneous action of C4, C6 and C8 lactones was observed. The data obtained give grounds for assumption, that bacteria may use exogenous lactones, including those produced by closely related bacteria, during their life cycle.     

The Evolutionary Origins of Detoxifying Enzymes: THE MAMMALIAN SERUM PARAOXONASES (PONs) RELATE TO BACTERIAL HOMOSERINE LACTONASES*

Serum paraoxonases (PONs) are detoxifying lactonases that were first identified in mammals. Three mammalian families are known, PON1, 2, and 3 that reside primarily in the liver. They catalyze essentially the same reaction, lactone hydrolysis, but differ in their substrate specificity. Although some members are highly specific, others have a broad specificity profile. The evolutionary origins and substrate specificities of PONs therefore remain poorly understood. Here, we report a newly identified family of bacterial PONs, and the reconstruction of the ancestor of the three families of mammalian PONs. Both the mammalian ancestor and the characterized bacterial PONX_OCCAL were found to efficiently hydrolyze N-acyl homoserine lactones that mediate quorum sensing in many bacteria, including pathogenic ones. The mammalian PONs may therefore relate to a newly identified family of bacterial, PON-like “quorum-quenching” lactonases. The appearance of PONs in metazoa is likely to relate to innate immunity rather than detoxification. Unlike the bacterial PON, the mammalian ancestor also hydrolyzes, with low efficiency, lactones other than homoserine lactones, thus preceding the detoxifying functions that diverged later in two of the three mammalian families. The bifunctionality of the mammalian ancestor and the trade-off between the quorum-quenching and detoxifying lactonase activities explain the broad and overlapping specificities of some mammalian PONs versus the singular specificity of others.     

Biological activities of sesquiterpene lactones

Sesquiterpene lactones are characteristic constituents of the Compositae but also occur sporadically in other angiosperm families and even in some liverworts. These bitter substances often contain as a major structural feature an α,β-unsaturated-γ-lactone, which in recent studies has been shown to be associated with anti-tumor, cytotoxic, anti-microbial and phytotoxic activity. They are known to poison livestock, to act as insect feeding deterrents and to cause allergic contact dermatitis in humans. This review highlights the present state of knowledge on the biological activities and mechanism of action of some sesquiterpene lactones.     

Species-specific responses of dew fly larvae to mycotoxins

Abstract   The larval stages of saprophagous insects and filamentous fungi have been demonstrated to be serious competitors on decaying organic matter. When filamentous fungi appear to be competitively superior, fungal mycotoxins have frequently been suggested to constitute chemical weapons, causing high mortality among insect larvae. In this study, we tested whether typical fungal secondary compounds can indeed be considered as the underlying mechanism of interference competition between filamentous fungi and various saprophagous Drosophila species. In contrast to our expectation, we found no grand mycotoxin-specific effects, but insect survival appeared to be generally determined by complex interaction between toxin identity, toxin concentration and insect species. Three out of five drosophilids seemed to be equally affected by the mycotoxins used in this study, whereas two species showed toxin-specific changes in survival. Only two (Kojic acid and Ochratoxin A) out of seven mycotoxins caused insect-specific responses. Moreover, we discovered correlations between survival in toxin-free and spoiled substrates, which may indicate an interrelationship between intra-specific competitive ability and resistance to mycotoxins. We discuss the significance of mycotoxins as underlying mechanisms driving competitive insect–fungus interactions.