Abstract
Antimicrobial peptides (AMPs) are an alternative group for the therapy of infectious diseases, with activity against a wide range of diverse pathogens. However, classical AMPs have significant side effects in human cells due to their unspecific pore formation in biomembranes. Nevertheless, AMPs are promising therapeutics and can be isolated from natural sources, which include sea and freshwater molluscs. The AMPs identified in these organisms show promising antimicrobial activities, as pathogens are mainly fought by innate defence mechanisms. An auspicious candidate among molluscs is the Cuban freshwater snail Pomacea poeyana, from which the peptides Pom-1 and Pom-2 have been isolated and studied. These studies revealed significant antimicrobial activities for both AMPs. Based on the activities determined, Pom-1 was used for further optimization. In order to meet the emerging requirements of improved anti-biofilm activity against naturally occurring Candida species, the six derivatives Pom-1A to F were developed and investigated. Analysis of the derivatives acting on the most abundant naturally occurring Candida yeast Candida albicans (C. albicans) revealed a strong anti-biofilm activity, especially induced by Pom-1 B, C, and D. Furthermore, a moderate decrease in the metabolic activity of planktonic yeast cells was observed.
Highlights
A more than considerable amount of 75% of all women contract a fungal infection with the pathogenic genus Candida, like C. parapsiolosis, C. glabrata, or C. tropicalis, during their lifetime
To determine the antifungal effect of the peptide derivatives on planktonic C. albicans cells, different concentrations (2.5–20 μg/mL) of the peptides were applied to fixed cell numbers (2.5 × 103 cells per well) and were incubated for 24 h in a suspension microtiter plate
Clinical strains of C. albicans reach a minimum inhibitory concentration (MIC) of 0.5 to 64 μg/mL to fluconazole, 0.03 to 16 μg/mL to intraconazole, and 0.125 to 4 μg/mL to amphotericin-B, which is considered as the golden standard for candidiasis [9,37,38,39]
Summary
A more than considerable amount of 75% of all women contract a fungal infection with the pathogenic genus Candida, like C. parapsiolosis, C. glabrata, or C. tropicalis, during their lifetime. Many microorganisms, including yeast, form biofilms attached to abiotic and biotic surfaces. Proliferate, and produce an extracellular matrix (ECM) forming microcolonies that mature (Figure 1). Cells disperse from the mature biofilms that adhere to surfaces and start a new cycle of biofilm formation [2]. This mechanism is a strategy of yeast cells to increase their physical stability to antifungal drugs, increasing the morbidity and mortality of infected patients [3,4,5,6,7]
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