Screening clinical Candida albicans isolates for invasiveness by mimicking the human environment

Abstract

ObjectivesCandida albicans colonizes a wide range of human body niches, but also causes severe invasive infections, such as candidemia. No screening method exists to predict which colonizer may lead to invasive infections. Invasiveness and virulence are associated with yeast filamentation, triggered by environmental factors encountered in the host. Here, we monitored the filamentation profile and colony appearance time of a C.albicans strain isolated from a patients abscess. Using eight additional C.albicans clinical isolates, we established an in vitro screening-framework of filamentation to assess the invasiveness potential of individual isolates. MethodsWe monitored the filamentation pattern of nine C.albicans clinical isolates over 14 days in 48 environmental conditions, including combinations of glucose/nitrogen concentrations, pH and temperature, to mimic host environment variations. Additionally, we tested invasiveness by growing isolates on modified filtration membranes, mimicking physical human body barriers usually colonized by Candida. An automated image analysis pipeline was developed to quantify filamentation. ResultsTwo types of colony filamentation morphology were differentiated, star and hazy. The total filamentation area depended on environmental factors. Based on their filamentation response to environmental changes, the isolates clustered in three distinct groups reflecting their site of isolation in the host. We moreover found that filamentation morphologies on modified filtration membranes could be predictors of invasiveness. ConclusionThis work lays the ground for screening assays, which could help assessing the potential of a colonizing Candida isolate to cause invasive disease, paving the way for tailored preventive therapy regimens in the future.