engleski

Antivirulence strategies against medically important Candida spp.

Since the well-known physiological way of disruption of life cycle of medically important fungi by active substances currently registered as medicines and consequently the emerging of resistance to such medicines, the new paradigmatic shift at microbial target started. Knowing the complex life of Candida spp. and interaction between the host’s attributes are possible way to find a new target for medicines. Since we know the atributes of fungal virulence and steps during interaction between the host’s factors, we could modulate those complex systems. The yeast such such as Candida spp. are as the most potent target for such a research. New strategies towards eradication or prevention of fungal infection include inhibition of adherence to biological and non-biological surafces, such as catheters or implants by modulation of cell-curface hydrophobicity (CSH) and modulation of surface-based receptors. Small molecular weight inhibitory molecules against yeast germination and with inhibitory activity against hydrolitic enzymes such as proteases and phospholipases are also in antifungal medicines pipeline. New strategies include also new targets in yeast cells. Fungicidal activity of ROSproducing molecules or nanoparticles, modulation of not well studied steps in survival and fitness of yeast cells in host (modulation of calcineurin or Hsp90 or sphinglipid sythesis pathways) ; application of specific monoclonal antibodies or radioimmunotherapy ; potentisation of known antifungals with molecules not indicated for fungals infection (statins, NSAIDs) are examples of novel targets. The use of synthetic peptides (antimicrobial peptides, AMP) or those derived from human source (defensins, histatins) against fungal infection are in late clinical phases. Many medicines express also antifungal activity against medically important fungi and such medicines could be repurposed (verapamil, rifampin, rapamycin etc.). Besides the improvents of current antifungals by structural modification brand new paradigmatic research area emerge within the antifungal pipeline. During the presentation examples of methodological approach in vitro and examples of novel molecules together with a clinical outcome will be given. REFERENCES: 1. J. R. Perfect (2017) Nature Reviews Drug Discovery, 16: 603-616 2. I. Zorić, I. Kosalec et al. (2017) BMC Complement Altern. Med. 17

virulence ; candida

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