Infection and Drug Resistance · 2020 · 60 citations · 23 references
Life SciencesInfectious DiseasesMicrobiologyAntimicrobial ResistanceMedical MicrobiologyMicrobial PathogenesisAntifungal AgentsAntifungal ResistanceAntifungal TherapyAntimicrobial PeptidesFungal Cell BiologyFungal PathogenesisAntifungal PeptidesAntifungal TreatmentsAntimicrobial Peptide ActivityCandida Albicans InfectionCell Wall PermeabilityCell Wall Synthesis InhibitionFungal Cell Wall Targeting DrugsNew Antifungal Agents
Background: Candida albicans is associated with high mortality among immunocompromised patients. Resistance to and toxic side effects of antifungal drugs require the development of alternative antifungal agents. AMP-17 is a novel antimicrobial peptide derived from Musca domestica that exerts excellent antifungal effects against the Candida species. In this article, we discuss the potential mechanism of AMP-17 against C. albicans from the perspective of affecting the latter’s cell external structure. Methods: Recombinant AMP-17 was prepared by prokaryotic expression system, and its anti- C. albicans activity was detected by microdilution method. Microscopy and scanning electron microscopy were used to examine morphological changes in C. albicans . Cell wall-specific staining method was used to detect the change of cell wall integrity of C. albicans after AMP-17 treatment. AMP-17-induced damage to the C. albicans cell membrane was analyzed by fluorescent probes and glycerol assay kit. The expression of genes related to fungal cell wall and cell-membrane synthesis was detected by qRT-PCR. Results: Morphological observations showed that the growth of C. albicans was significantly inhibited in AMP-17-treated cells; the cells appeared aggregated and dissolved, with severe irregularities in shape. Furthermore, AMP-17 damaged the integrity of C. albicans cell walls. The cell wall integrity rate of AMP-17-treated cells was only 21.7% compared to untreated cells. Moreover, the change of membrane dynamics and permeability suggested that the cell membrane was disrupted by AMP-17 treatment. Genetic analysis showed that after AMP-17 treatment, the cell wall synthesis-related gene FKS2 of C. albicans was up-regulated 3.46-fold, while the cell membrane ergosterol synthesis-related genes ERG1, ERG5, ERG6 , and MET6 were down-regulated 5.88-, 17.54-, 13.33-, and 7.14-fold, respectively. Conclusion: AMP-17 treatment disrupted the cell wall integrity and membrane structure of C. albicans and is likely a novel therapeutic option for prevention and control of C. albicans infections. Keywords: AMP-17, C. albicans , cell wall, membrane dynamics and permeability
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