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抗 CR3-RP 多克隆抗体对耐多药真菌病原体耳念珠菌生物膜的活性。

Activity of anti-CR3-RP polyclonal antibody against biofilms formed by Candida auris, a multidrug-resistant emerging fungal pathogen.

机构信息

Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 84215, Bratislava, Slovakia.

Department of Biology and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, 78249, USA.

出版信息

Eur J Clin Microbiol Infect Dis. 2019 Jan;38(1):101-108. doi: 10.1007/s10096-018-3400-x. Epub 2018 Oct 16.

Abstract

Fungal biofilm has remained a serious medical problem that complicates treatment of mycoses. In particular, once biofilms are formed, they display high levels of resistance against most common antifungals. Candida auris is currently considered as a serious emerging fungal pathogen frequently exhibiting high levels of resistance to antifungals. Recent studies have confirmed that C. auris shares similarity with Candida albicans in regards to virulence-associated proteins involved in adherence and biofilm development. Complement receptor 3-related protein (CR3-RP) is one of the key surface antigens expressed by Candida species during biofilm formation. Here, we have investigated the presence of this cell surface moiety on the surface of C. auris, as well as the potential of anti-CR3-RP polyclonal antibody (Ab) to inhibit biofilm formation by this emerging fungal pathogen. Using indirect immunofluorescence and ELISA, we were able to confirm the presence of CR3-RP in C. auris cells within biofilms. Further, not only anti-CR3-RP Ab was able to inhibit biofilm formation by multiple C. auris strains when added during the adherence phase, but it also demonstrated activity against C. auris 24-h pre-formed biofilms, which compared favorably to levels of inhibition achieved by treatment with current conventional antifungals fluconazole, amphotericin B, and caspofungin. Overall, our data demonstrate the presence of this antigen on the surface of C. auris and points to the potential of anti-CR3-RP Ab in eradication of biofilms formed by this novel fungal pathogen.

摘要

真菌生物膜仍然是一个严重的医学问题,使真菌感染的治疗变得复杂。特别是,一旦生物膜形成,它们对大多数常用抗真菌药物表现出高水平的耐药性。耳念珠菌目前被认为是一种严重的新兴真菌病原体,经常表现出高水平的抗真菌药物耐药性。最近的研究证实,耳念珠菌在与粘附和生物膜形成相关的毒力相关蛋白方面与白色念珠菌相似。补体受体 3 相关蛋白(CR3-RP)是念珠菌属在生物膜形成过程中表达的关键表面抗原之一。在这里,我们研究了这种细胞表面成分在耳念珠菌表面的存在情况,以及抗 CR3-RP 多克隆抗体(Ab)抑制这种新兴真菌病原体生物膜形成的潜力。通过间接免疫荧光和 ELISA,我们能够确认 CR3-RP 存在于生物膜内的耳念珠菌细胞中。此外,抗 CR3-RP Ab 不仅能够在粘附阶段添加时抑制多种耳念珠菌菌株的生物膜形成,而且还能够抑制耳念珠菌 24 小时预先形成的生物膜,其抑制水平与当前常规抗真菌药物氟康唑、两性霉素 B 和卡泊芬净相当。总体而言,我们的数据表明这种抗原存在于耳念珠菌表面,并指出抗 CR3-RP Ab 在根除这种新型真菌病原体形成的生物膜方面的潜力。

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