Didehydroroflamycoin pentaene macrolide family from Streptomyces durmitorensis MS405(T): production optimization and antimicrobial activity

AimsThe aim of this study was to improve production of pentaene 32,33-didehydroroflamycoin (DDHR) in Streptomyces durmitorensis MS405 strain to obtain quantities sufficient for in depth analysis of antimicrobial properties. Methods and ResultsThrough classical medium optimization conditions for stable growth, DDHR production within 7days of incubation was established. Yields of 215mgl(-1) were achieved in shake flask experiments in complex medium with mannitol as the primary carbon source. DDHR had poor antibacterial activity with minimal inhibitory concentrations (MIC) of 400gml(-1) for Staphylococcus aureus and Bacillus subtilis, while MIC of 70gml(-1) was determined for Candida albicans. Using flow cytometry and fluorescent microscopy, it was demonstrated that DDHR induced membrane damage in C.albicans followed by cell death. Combination studies with known antifungal nystatin showed that DDHR is a promising agent for the development of novel antimycotic treatments potentially less toxic for human cells. ConclusionsPentaene didehydroroflamycoin has no antibacterial activity but can be further developed for the application in antifungal therapy. Significance and Impact of the StudyThis study is the first report on the stable and production in high yields of a novel pentaene family that acts on Candida cell membranes and can be used in combination with known antifungals. Polyenes are still antifungal antibiotics of choice, and therefore, isolation and production of new lead structures are highly significant

Fibrinolysis in Acute and Chronic Cardiovascular Disease

The formation of an obstructive thrombus within an artery remains a major cause of mortality and morbidity worldwide. Despite effective inhibition of platelet function by modern antiplatelet therapies, these agents fail to fully eliminate atherothrombotic risk. This may well be related to extensive vascular disease, beyond the protective abilities of the treatment agents used. However, recent evidence suggests that residual vascular risk in those treated with modern antiplatelet therapies is related, at least in part, to impaired fibrin clot lysis. In this review, we attempt to shed more light on the role of hypofibrinolysis in predisposition to arterial vascular events. We provide a brief overview of the coagulation system followed by addressing the role of impaired fibrin clot lysis in acute and chronic vascular conditions, including coronary artery, cerebrovascular, and peripheral vascular disease. We also discuss the role of combined anticoagulant and antiplatelet therapies to reduce the risk of arterial thrombotic events, addressing both efficacy and safety of such an approach. We conclude that impaired fibrin clot lysis appears to contribute to residual thrombosis risk in individuals with arterial disease on antiplatelet therapy, and targeting proteins in the fibrinolytic system represents a viable strategy to improve outcome in this population. Future work is required to refine the antithrombotic approach by modulating pathological abnormalities in the fibrinolytic system and tailoring therapy according to the need of each individual