期刊
JOURNAL OF FUNGI
卷 6, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/jof6030141
关键词
Penicillium chrysogenum antimicrobial protein C; PAFC; exudate; Candida albicans; reactive oxygen species; plasma membrane permeabilization; cell death
资金
- Austrian Science FundFWF [I3132-B21]
- FWF
- Scholarship of the Aktion Osterreich-Ungarn
- Postdoctoral Excellence Programme [PD 135248]
- bilateral Austrian-Hungarian Joint Research Project [ANN 131341]
- Hungarian National Research, Development and Innovation (NKFIH) Office
- Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [UNKP-20-5]
- New National Excellence Program of the Ministry for Innovation and Technology (ITM)
- NKFIH Office [GINOP-2.3.2-15-2016-00014, 20391-3/2018/FEKUSTRAT, TUDFO/47138-1/2019-ITM FIKP, RTI2018-101115B-C21]
- Ministerio de Ciencia, Innovacion, y Universidades (Spain) (MICINN/FEDER Funds)
Small, cysteine-rich and cationic antimicrobial proteins (AMPs) from filamentous ascomycetes promise treatment alternatives to licensed antifungal drugs. In this study, we characterized the Penicillium chrysogenum Q176 antifungal protein C (PAFC), which is phylogenetically distinct to the other two Penicillium antifungal proteins, PAF and PAFB, that are expressed by this biotechnologically important ascomycete. PAFC is secreted into the culture broth and is co-expressed with PAF and PAFB in the exudates of surface cultures. This observation is in line with the suggested role of AMPs in the adaptive response of the host to endogenous and/or environmental stimuli. The in silico structural model predicted five beta-strands stabilized by four intramolecular disulfide bonds in PAFC. The functional characterization of recombinant PAFC provided evidence for a promising new molecule in anti-Candida therapy. The thermotolerant PAFC killed planktonic cells and reduced the metabolic activity of sessile cells in pre-established biofilms of two Candida albicans strains, one of which was a fluconazole-resistant clinical isolate showing higher PAFC sensitivity than the fluconazole-sensitive strain. Candidacidal activity was linked to severe cell morphology changes, PAFC internalization, induction of intracellular reactive oxygen species and plasma membrane disintegration. The lack of hemolytic activity further corroborates the potential applicability of PAFC in clinical therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据