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The resistance of biofilms to conventional antibiotics complicates the treatment of chronic cystic fibrosis (CF). We investigated the effects of peptoids, peptides, and conventional antibiotics on the biomass and cell viability within Pseudomonas aeruginosa biofilms. At their MICs, peptoids 1 and 1-C13(4mer) caused maximum reductions in biomass and cell viability, respectively. These results suggest that peptoids of this class could be worth exploring for the treatment of pulmonary infections occurring in CF patients.

Background: Aspergillus niger is an ascomycetous fungus that is known to reproduce through asexual spores, only. Interestingly, recent genome analysis of A. niger has revealed the presence of a full complement of functional genes related to sexual reproduction 1. An example of such genes are the dioxygenase genes which in Aspergillus nidulans, have been shown to be connected to oxylipin production and regulation of both sexual and asexual sporulation 234. Nevertheless, the presence of sex related genes alone does not confirm sexual sporulation in A. niger., Results: The current study shows experimentally that A. niger produces the oxylipins 8,11-dihydroxy octadecadienoic acid (8,11-diHOD), 5,8-dihydroxy octadecadienoic acid (5,8-diHOD), lactonized 5,8-diHOD, 8-hydroxy octadecadienoic acid (8-HOD), 10-hydroxy octadecadienoic acid (10-HOD), small amounts of 8-hydroxy octadecamonoenoic acid (8-HOM), 9-hydroxy octadecadienoic acid (9-HOD) and 13-hydroxy octadecadienoic acid (13-HOD). Importantly, this study shows that the A. niger genome contains three putative dioxygenase genes, ppoA, ppoC and ppoD. Expression analysis confirmed that all three genes are indeed expressed under the conditions tested., Conclusion: A. niger produces the same oxylipins and has similar dioxygenase genes as A. nidulans. Their presence could point towards the existence of sexual reproduction in A. niger or a broader role for the gene products in physiology, than just sexual development.

Oxylipins are associated with important processes of the fungal life cycle, such as spore formation. Here, we report the formation of FA metabolites in Agaricus bisporus. Incubation of a crude extract of lamellae with linoleic acid (18:2) led to the extensive formation of two oxylipins. They were identified as 8(R)-hydroxy-9Z,12Z-octadecadienoic acid (8-HOD) and 8(R),11 (S)-dihydroxy-9Z,12Z-octadecadienoic acid (8,11-diHOD) by using RP-HPLC, GC-MS, IR, GC-MS analysis of diastereomeric derivatives, and 1H NMR and 13C NMR spectroscopy. Neither compound has been reported before in A. bisporus. Oleic (18:1), alpha-linolenic (18:3n-3), and gamma-linolenic (18:3n-6) acids were converted into their 8-hydroxy derivatives as well, and 18:3n-3 was further metabolized to its 8,11-diol derivative. Reactions with [U-13C]18:2 demonstrated that the compounds 8-HOD and 8,11-diHOD were formed from exogenously supplied 18:2. When [U-13C]8-HOD was supplied, it was not converted into 8,11-diHOD, indicating that it was not an intermediate in the formation of 8,11-diHOD. When a crude extract of A. bisporus was incubated under an atmosphere of 16O2/18O2, the two hydroxyl groups of 8,11-diHOD contained either two 180 atoms or two 60 atoms. Species that contained one of each isotope could not be detected. We propose that the formation of the 8,11-dihydroxy compounds occurs through either an 8,11-endoperoxy, an 8-peroxo free radical, or an 8-hydroperoxy intermediate. In the latter case, the reaction should be catalyzed by dioxygenase with novel specificity.

Type 1 vanilloid receptors (VR1) have been identified recently in the brain, in which they serve as yet primarily undetermined purposes. The endocannabinoid anandamide (AEA) and some of its oxidative metabolites are ligands for VR1, and AEA has been shown to afford protection against ouabain-induced in vivo excitotoxicity, in a manner that is only in part dependent on the type 1 cannabinoid (CB1) receptor. In the present study, we assessed whether VR1 is involved in neuroprotection by AEA and by arvanil, a hydrolysis-stable AEA analog that is a ligand for both VR1 and CB1. Furthermore, we assessed the putative involvement of lipoxygenase metabolites of AEA in conveying neuroprotection. Using HPLC and gas chromatography/mass spectroscopy, we demonstrated that rat brain and blood cells converted AEA into 12-hydroxy-N-arachidoylethanolamine (12-HAEA) and 15-hydroxy-N-arachidonoylethanolamine (15-HAEA) and that this conversion was blocked by addition of the lipoxygenase inhibitor nordihydroguaiaretic acid. Using magnetic resonance imaging we show the following: (1) pretreatment with the reduced 12-lipoxygenase metabolite of AEA, 12-HAEA, attenuated cytotoxic edema formation in a CB1 receptor-independent manner in the acute phase after intracranial injection of the Na+/K+-ATPase inhibitor ouabain; (2) the reduced 15-lipoxygenase metabolite, 15-HAEA, enhanced the neuroprotective effect of AEA in the acute phase; (3) modulation of VR1, as tested using arvanil, the VR1 agonist capsaicin, and the antagonist capsazepine, leads to neuroprotective effects in this model, and arvanil is a potent neuroprotectant, acting at both CB1 and VR1; and (4) the in vivo neuroprotective effects of AEA are mediated by CB1 but not by lipoxygenase metabolites or VR1.