Streptomyces are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may thrive on their own in the soil, or associate with other organisms, such as plants or invertebrates. Some soil-derived strains exhibit hemolytic properties when cultivated on blood agar, raising the question of whether hemolysis could be a virulence factor of the bacteria. In this work we examined hemolytic compound production in 23 β-hemolytic Streptomyces isolates; of these 12 were soil-derived, 10 were arthropod-associated, and 1 was plant-associated. An additional human-associated S. sp. TR1341 served as a control. Mass spectrometry analysis suggested synthesis of polyene molecules responsible for the hemolysis: candicidins, filipins, strevertene A, tetrafungin, and tetrin A, as well as four novel polyene compounds (denoted here as polyene A, B, C, and D) in individual liquid cultures or paired co-cultures. The non-polyene antifungal compounds actiphenol and surugamide A were also identified. The findings indicate that the ability of Streptomyces to produce cytolytic compounds (here manifested by hemolysis on blood agar) is an intrinsic feature of the bacteria in the soil environment and could even serve as a virulence factor when colonizing available host organisms. Additionally, a literature review of polyenes and non-polyene hemolytic metabolites produced by Streptomyces is presented.
Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion-pairing of cationic SkQ1+ with free fatty acid anions resulting in uncoupling; ii) SkQ1H2 ability to interact with lipoperoxyl radical; iii) interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Qi), involving the reduction of SkQ1 to SkQ1H2 by ubiquinol. We elucidated SkQ1 antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (Jm) and cytosolic H2O2 (Jc) release rates in HepG2 cells. Only in glycolytic cells, SkQ1 prevented the rotenone-induced enhancement of Jm and Jc but not basal releases without rotenone. The effect ceased in glutaminolytic aglycemic cells, in which the redox parameter NAD(P)H/FAD increased after rotenone in contrast to its decrease in glycolytic cells. Autofluorescence decay indicated decreased NADPH/NADH ratios with rotenone in both metabolic modes. SkQ1 did not increase cell respiration and diminished Jm established high by antimycin or myxothiazol but not by stigmatellin. The revealed SkQ1 antioxidant modes reflect its reduction to SkQ1H2 at Complex I IQ or Complex III Qi site. Both reductions diminish electron diversions to oxygen thus attenuating superoxide formation. Resulting SkQ1H2 oxidizes back to SkQ1at the second (flavin) Complex I site, previously indicated for MitoQ10. Regeneration proceeds only at lower NAD(P)H/FAD in glycolytic cells. In contrast, cyclic SkQ1 reduction/SkQ1H2 oxidation does not substantiate antioxidant activity in intact cells in the absence of oxidative stress (neither pro-oxidant activity, representing a great advantage). A targeted delivery to oxidative-stressed tissues is suggested for the effective antioxidant therapy based on SkQ1.
- MeSH
- antimycin A analogy a deriváty farmakologie MeSH
- antioxidancia farmakologie MeSH
- buňky Hep G2 MeSH
- flavinadenindinukleotid metabolismus MeSH
- glykolýza MeSH
- lidé MeSH
- methakryláty farmakologie MeSH
- mitochondrie účinky léků metabolismus MeSH
- NAD metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres MeSH
- oxidativní fosforylace * MeSH
- plastochinon analogy a deriváty farmakologie MeSH
- polyeny farmakologie MeSH
- respirační komplex I metabolismus MeSH
- respirační komplex III metabolismus MeSH
- rotenon farmakologie MeSH
- superoxidy metabolismus MeSH
- thiazoly farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Macrolide antibiotics such as azithromycin or clarithromycin are known to have potent anti-inflammatory and immunomodulatory effects but these properties cannot be widely used due to a risk of bacterial resistance. We studied another polyketide antibiotic, structurally related manumycin A known as a streptomycete derived farnesyltransferase inhibitor with limited antibacterial effects, with respect to its potential regulation of mRNA expression of several genes associated with proinflammatory responses. Downregulation of mRNA for IL-6, TLR-8, IL-1 beta and IL-10 was found in THP-1 cells after 4h stimulation with TNF alpha in the presence of manumycin A and downregulated TLR-8 and EGR-1 genes were observed after 8h. Among the genes upregulated in response to manumycin were HMOX-1, TNFRSF10A, IL-1R1, TICAM2, NLRP12 after 4h and only IL-1R1 after 8h. Furthermore, manumycin A was found to inhibit IL-1beta, IL-6, and IL-8 production in TNF alpha stimulated THP-1 cells and peripheral blood monocytes in a dose dependent manner (0.25-1 μM of manumycin A) without affecting cell viability. Cell viability of blood monocytes decreased by about 30% at manumycin A doses of 2-5 μM. Manumycin A also inhibited IL-18 release from THP-1 cells, while in cultures of blood monocytes, this cytokine was not detectable. That manumycin A mediated downregulation of proinflammatory genes in human monocytes confirmed by a measurement of cytokine levels in culture supernatants, together with a very limited effect on cell viability, might suggest potential anti-inflammatory properties of this polyketide antibiotic.
- MeSH
- antibakteriální látky farmakologie MeSH
- antiflogistika farmakologie MeSH
- buněčné linie MeSH
- cytokiny genetika metabolismus MeSH
- imunomodulace MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- monocyty účinky léků imunologie MeSH
- polyeny farmakologie MeSH
- polynenasycené alkamidy farmakologie MeSH
- protein 1 časné růstové odpovědi genetika metabolismus MeSH
- receptory interleukinu-1 genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- TNF-alfa metabolismus MeSH
- toll-like receptor 8 genetika metabolismus MeSH
- zánět farmakoterapie imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- alylaminy,
- MeSH
- allylamin farmakologie klasifikace terapeutické užití MeSH
- antifungální látky farmakologie klasifikace terapeutické užití MeSH
- azoly farmakologie klasifikace terapeutické užití MeSH
- dermatologické látky farmakologie MeSH
- farmakopea jako téma MeSH
- lidé MeSH
- polyeny farmakologie klasifikace terapeutické užití MeSH
- Check Tag
- lidé MeSH
Within the complex network of chemical signals used by termites, trail pheromones and sex pheromones are among the best known. Numerous recent papers map the chemical identity and glandular origin of these pheromones in nearly all major isopteran taxa. In this study, we aimed to describe the sex pheromone and the trail pheromone of a poorly known sand termite, Psammotermes hybostoma. We identified (3Z,6Z,8E)-dodeca-3,6,8-trien-1-ol (dodecatrienol) as the sex pheromone released by tergal and sternal glands of female imagos and, at the same time, as the trail pheromone secreted from the sternal gland of workers. We conclude that chemical communication in Psammotermes does not differ from that of most other Rhinotermitidae, such as Reticulitermes, despite the presence of a diterpene as a major component of the trail pheromone of Prorhinotermes to which Psammotermes is presumed to be phylogenetically close. Our findings underline once again the conservative nature of chemical communication in termites, with dodecatrienol being a frequent component of pheromonal signals in trail following and sex attraction and, at the same time, a tight evolutionary relationship between the trail following of working castes and the sex attraction of imagos.
- MeSH
- Isoptera chemie účinky léků metabolismus MeSH
- polyeny analýza farmakologie MeSH
- sexuální chování zvířat účinky léků MeSH
- sexuální lákadla chemie metabolismus farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- aspergilóza farmakoterapie MeSH
- azoly aplikace a dávkování farmakologie MeSH
- echinokandiny aplikace a dávkování farmakologie MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- modely u zvířat MeSH
- polyeny aplikace a dávkování farmakologie MeSH
- techniky in vitro MeSH
- výsledek terapie MeSH
- záchranná terapie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinické zkoušky MeSH
- MeSH
- antibakteriální látky terapeutické užití MeSH
- antifungální látky * terapeutické užití MeSH
- antiinfekční látky lokální terapeutické užití MeSH
- atopická dermatitida MeSH
- azoly farmakologie terapeutické užití MeSH
- Candida albicans * izolace a purifikace patogenita MeSH
- dezinficiencia terapeutické užití MeSH
- diferenciální diagnóza MeSH
- infekční nemoci kůže etiologie terapie MeSH
- klinický obraz nemoci MeSH
- koinfekce komplikace terapie MeSH
- kultivační techniky využití MeSH
- lidé MeSH
- orální kandidóza * diagnóza etiologie terapie MeSH
- polyeny farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
