Physiological and oxidative stress responses of lettuce to cleomside A: a thiohydroximate, as a new allelochemical from Cleome arabica L.

The inclination toward natural products have led the onset for the discovery of new bioactive metabolites that could be targeted for specific therapeutic or agronomic applications. This study aimed to isolate bioactive compounds from Cleome arabica L., and subsequently determine the unexplored mechanism of action of the newly identified compounds on Lactuca sativa L. Chemical investigation of the ethyl acetate fraction of methanolic silique extract of C. arabica afforded seven secondary metabolites belonging to different classes such as flavonoids, triterpene, and a new thiohydroximate derivative, named cleomside A. Among phytotoxic assays, the growth of lettuce was totally inhibited by cleomside A compared to the other identified compounds. This effect was associated with the increased levels of electrolyte leakage, malondialdehyde, and hydrogen peroxide indicating disruption of membrane integrity and induction of oxidative stress. Activities of the antioxidant enzymes SOD, CAT, and APX were also elevated, thereby demonstrating the enhanced generation of reactive oxygen species upon identified allelochemical exposure. Thus, the changes caused by cleomside A described herein can contribute to better understanding the allelochemical actions of thiohydroximate and the potential use of these substances in the production of natural herbicides compared to the other identified flavonoids and triterpene

Assembly of the Auditory Circuitry by a Hox Genetic Network in the Mouse Brainstem

Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem

Herbicidal potential of ophiobolins produced by Drechslera gigantea

Drechslera gigantea, a potential mycoherbicide of grass weeds, was isolated in Florida from naturally infected large crabgrass (Digitaria sanguinalis); it produces phytotoxic metabolites in liquid culture. The main metabolite was identified by spectroscopic methods and optical properties as ophiobolin A (1), a well-known phytotoxic sesterterpene produced by several phytopathogenic fungi of important crops and already extensively studied for its interesting biological activities. The other three minor metabolites proved to be related to ophiobolin A and were identified using the same techniques as 6-epi-ophiobolin A and 3-anhydro-6-epi-ophiobolin A (2 and 3) and ophiobolin I (4). Assayed on punctured detached leaves of several grass and dicotyledon weeds, ophiobolin A proved to be on average more phytotoxic as compared to the other related compounds. Some structural features appear to be important for the phytoxicity, such as the hydroxy group at C-3, the stereochemistry at C-6, and the aldehyde group at C-7. Furthermore, grass weeds usually proved to be more sensitive to the phytotoxins than dicotyledons, on which ophiobolin A caused the appearance of large necrosis even at the lowest concentration assayed. This is the first report about the production of ophiobolins from D. gigantea and of the proposed use as potential natural herbicides against grass weeds. © 2006 American Chemical Society

Drazepinone, a trisubstituted tetrahydronaphthofuroazepinone with herbicidal activity produced by Drechslera siccans

When grown in a minimal-defined medium, a strain of Drechslera siccans, a pathogenic fungus isolated from seeds of Lolium perenne, produced phytotoxic metabolites. This strain is one of the best toxin producers among several grass pathogenic fungal strains collected and tested to find phytotoxins to be used as natural herbicides of monocot weeds. From the culture filtrates of D. siccans, we isolated a new phytotoxic trisubstituted naphthofuroazepinone, named drazepinone, and characterised it as a 3,5,12a-trimethyl-2,5,5a,12a-tetrahydro- 1H-naphtho[2′,3′:4,5]furo[2,3-b]azepin-2-one. Assayed at 2 μg μl-1 solution the novel metabolite proved to have broad-spectrum herbicidal properties, without antibacterial and antifungal activities, and low zootoxic activity. Its original chemical structure and the interesting biological properties make drazepinone a potential natural herbicide. © 2005 Elsevier Ltd. All rights reserved

Ophiobolin E and 8-epi-ophiobolin J produced by Drechslera gigantea, a potential mycoherbicide of weedy grasses

Drechslera gigantea, a fungal pathogen isolated from large crabgrass (Digitaria sanguinalis) and proposed as a potential mycoherbicide of grass weeds, produces phytotoxic metabolites in liquid and solid cultures. Ophiobolin A and three minor ophiobolins i.e., 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A and ophiobolin I were obtained from the liquid culture broths. Interestingly and unexpectedly, ophiobolins also appeared in cultures of this fungus and they were isolated together with the known ophiobolins B and J, and designed as ophiobolin E and 8-epi-ophiobolin J. They were characterized using essentially spectroscopic methods. It is noteworthy that D. gigantea produces such a plethora of bioactive organic substances. Some structure-activity relationship results are also discussed in this report. © 2006 Elsevier Ltd. All rights reserved

GC-MS-based metabolomics study of single-and dual-species biofilms of Candida albicans and Klebsiella pneumoniae

Candida albicans and Klebsiella pneumoniae frequently co-exist within the human host as a complex biofilm community. These pathogens are of interest because their association is also related to significantly increased morbidity and mortality in hospitalized patients. With the aim of highlighting metabolic shifts occurring in the dual-species biofilm, an untargeted GC-MS-based metabolomics approach was applied to single and mixed biofilms of C. albicans and K. pneumoniae. Metabolomic results showed that among the extracellular metabolites identified, approximately 40 compounds had significantly changed relative abundance, mainly involving central carbon, amino acid, vitamin, and secondary metabolisms, such as serine, leucine, arabitol, phosphate, vitamin B6, cyclo-(Phe-Pro), trehalose, and nicotinic acid. The results were related to the strict interactions between the two species and the different microbial composition in the early and mature biofilms

Naphthalenone polyketides produced by Neofusicoccum parvum , a fungus associated with grapevine Botriosphaeria dieback

A strain of Neofusicoccum parvum isolated from declining vines was pathogenic to grapevine cultivar Inzolia in Sicily. This strain produced some metabolites in liquid medium. Crude extract, through a bio-guided purification process, yielded four naphthalenone polyketides. They were identified by comparison with spectroscopic data and optical proprieties reported in literature as: (3S, 4S)-7-ethyl-3,4,8-trihydroxy-6-methoxy-3,4-dihydro-1-(2H)-naphthalenone, (3S*, 4S*)-3,4-dihydro-3,4,8-trihydroxy-7-(1-hydroxyethyl)-6-methoxy-1-(2H)-naphthalenone, (4S)-3,4-dihydro-4,8-dihydroxy-1-(2H)-naphthalenone, named botryosphaerones D and A, isosclerone, respectively, and (3S*,4S*)-3,4,5-trihydroxy-1-tetralone (1-4). Phytotoxic activity of the isolated compounds (1-4) was tested on grapevine leaves at using the leaf puncture assay. All tested compounds were phytotoxic, with botryosphaerone D showing the greatest activity. The phytotoxic effects decreased when treated leaves were exposed to light. All of the metabolites did not show in vitro antifungal activity against Diplodia seriata, Lasiodiplodia mediterranea, Neofusicoccum vitifusiforme, or Phytophthora citrophthora. This is the first report of in vitro production of botryosphaerones D and A, and 3,4,5-trihydroxy-1-tetralone by N. parvum

Antiviral Property of the Fungal Metabolite 3-O-Methylfunicone in Bovine Herpesvirus 1 Infection

Bovine herpesvirus type-1 (BoHV-1) is a widespread pathogen that provokes infectious rhinotracheitis and polymicrobial infections in cattle, resulting in serious economic losses to the farm animal industry and trade restrictions. To date, non-toxic active drugs against BoHV-1 are not available. The exploitation of bioactive properties of microbial products is of great pharmaceutical interest. In fact, fungi are a promising source of novel drugs with a broad spectrum of activities and functions, including antiviral properties. Hence, the potential antiviral properties of 3-O-methylfunicone (OMF), a secondary metabolite produced by Talaromyces pinophilus, were evaluated on BoHV-1. In this study, during BoHV-1 infection in bovine cells (MDBK), the non-toxic concentration of 5 µM OMF considerably reduced signs of cell death and increased cell proliferation. Furthermore, OMF significantly decreased the virus titer as well as the cytopathic effect and strongly inhibited the expression of bICP0, the major regulatory protein in the BoHV-1 lytic cycle. These findings were accompanied by a considerable up-regulation in the expression of the aryl hydrocarbon receptor (AhR), a multifunctional transcription factor also linked to the host’s response to a herpesvirus infection. Overall, our results suggest that by involving AhR, OMF shows potential against a BoHV-1 infection

Impact of the peptide wmr-k on dual-species biofilm candida albicans/klebsiella pneumoniae and on the untargeted metabolomic profile

In recent years, the scientific community has focused on the development of new antibiotics to address the difficulties linked to biofilm-forming microorganisms and drug-resistant infections. In this respect, synthetic antimicrobial peptides (AMPs) are particularly regarded for their therapeutic potential against a broad spectrum of pathogens. In this work, the antimicrobial and antibiofilm activities of the peptide WMR-K towards single and dual species cultures of Candida albicans and Klebsiella pneumoniae were investigated. We found minimum inhibitory concentration (MIC) values for WMR-K of 10 µM for K. pneumoniae and of 200 µM for C. albicans. Furthermore, sub-MIC concentrations of peptide showed an in vitro inhibition of biofilm formation of mono and polymicrobial systems and also a good biofilm eradication even if higher concentrations of it are needed. In order to provide additional evidence for the effect of the examined peptide, a study of changes in extracellular metabolites excreted and/or uptaken from the culture medium (metabolomic footprinting) in the poly-microbial association of C. albicans and K. pneumoniae in presence and absence of WMR-K was performed. Comparing to the untreated dual species biofilm culture, the metabolomic profile of the WMR-K treated culture appears significantly altered. The differentially expressed compounds are mainly related to the primary metabolic pathways, including amino acids, trehalose, pyruvic acid, glycerol and vitamin B6

In Vitro Evaluation of Antiviral Activities of Funicone-like Compounds Vermistatin and Penisimplicissin against Canine Coronavirus Infection

Recent studies have demonstrated that 3-O-methylfunicone (OMF), a fungal secondary metabolite from Talaromyces pinophilus belonging to the class of funicone-like compounds, has antiviral activity against canine coronaviruses (CCoV), which causes enteritis in dogs. Herein, we selected two additional funicone-like compounds named vermistatin (VER) and penisimplicissin (PS) and investigated their inhibitory activity towards CCoV infection. Thus, both compounds have been tested for their cytotoxicity and for antiviral activity against CCoV in A72 cells, a fibrosarcoma cell line suitable for investigating CCoV. Our findings showed an increase in cell viability, with an improvement of morphological features in CCoV-infected cells at the non-toxic doses of 1 μM for VER and 0.5 μM for PS. In addition, we observed that these compounds caused a strong inhibition in the expression of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor which is activated during CCoV infection. Our results also showed the alkalinization of lysosomes in the presence of VER or PS, which may be involved in the observed antiviral activities