On the role of cell wall proteins in the establishment of Candida infections
Year: 2017
Type: conference-paper
Abstract: Yeast species of the genus Candida are among the most frequent fungal causes of mucosal and life-threatening bloodstream infections in immunocompromised persons. Most frequently diagnosed are infections caused by C. albicans but during the last decade an increase in infections caused by other species such as C. glabrata and C. parapsilosis has been observed. Alarmingly, since a few years a new emerging multiresistant species - C. auris - is being identified worldwide with rapidly increasing frequence as the cause nosocomial systemic infections with high mortality rates. Being the first contact between pathogen and host, the cell wall of Candida plays an important role in the establishment of infections. At the same time, being an essential organelle and composed of fungal-specific components, cell walls represent ideal targets for development of novel antifungal therapies. The outer layer of the Candida cell wall is densely packed with GPI proteinswith a variety of different functions, several of which are directly implicated in fungal pathogenesis. For instance, attachment to human host tissues or abiotic medical devices and subsequent biofilm is mediated by cell wall-localized adhesins. Our laboratory focuses on identifying cell wall proteins of Candida and studying their role in the infection process. By analyzing wall proteomes of hyper-adhesive clinical isolates using mass spectrometry and comparison to reference strains, we tested whether these isolates display differential and increased incorporation of adhesins. In addition to a core proteome of about 20 proteins present in each strain under all analyzed conditions, proteomic analysis of hyperadherent C. glabrata and C. parapsilosis strains under biofilm-forming conditions showed (i) higher levels of adhesins that are also found in the reference strains and (ii) incorporation of novel adhesins that are not found in the reference strains. Thus, the hyperadhesive capacity of hyper-adherent Candida isolates seems to be correlated with increased and differential incorporation of cell wall adhesins. Current studies in ourlaboratory are aimed at performing functional and structural characterizations of the novel adhesins and other cell wall proteins to elucidate their role in primary host-pathogen interactions, antifungal drug resistance, and virulence.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7198360903