Programmpunkt

14:45

Titel: Phenotypic, genomic, and proteomic characteristics of biofilm-forming Candida parapsilosis lineages
ID: 11/EKV
Art: Abstractautor
Session: Workshop 02
Eukaryotic Pathogens incl. DMykG Lecture (FG EK)

Referent: Oliver Bader (Göttingen)


Abstract - Text

The human pathogenic yeast Candida parapsilosis has gained significant importance over the past decades as one of the principal causes of fungal bloodstream infections. Its capacity to adhere to host cells and clinically used abiotic surfaces (e.g. prostheses or catheters) is crucial during colonization processes and the establishment of infections. Isolates of C. parapsilosis are known to be able to switch between several different colony morphologies in vitro, which are correlated with different cell shapes and altered cell surface properties.

Prompted by a set of clinical specimen from a single patient that yielded stable smooth- as well as crepe-morphology lineages, we investigated the differences between five lineages and characterized the phenotypic spectrum as well as underlying mechanisms in >300 different-morphology clinical isolates.

In contrast to the initial assumption that the five different isolates were switched forms of an otherwise clonal strain, we confirmed by genome sequencing that the patient was colonized by at least three distinct lineages. Detailed statistical analysis placed the lineages distantly across the population of C. parapsilosis. Interestingly the Candidemia-associated blood culture isolate was of smooth morphology and matched with a nasal isolate of similar morphology; however the BC-isolate had undergone significant genomic rearrangements.

Next, we analyzed biofilm formation capacity and differences in morphotypes among several hundred clinical isolates which showed a multitude of phenotypic combinations, but no correlation with site of isolation became evident. Drug susceptibility profiles were altered between groups of biofilm-forming vs. non-forming isolates, and differences in colony morphology correlated with biofilm formation capacity and agar invasion, but not necessarily with virulence in a galleria mellonella infection model.

In addition to a core cell wall proteome consisting of carbohydrate-active enzymes, a set of adhesins was detected in the cell walls of selected hyperbiofilm-forming isolates by mass spectrometry. Downstream analyses showed distinct correlations of phenotypes such as altered virulence or morphology with adhesin incorporation.

Incorporation of specific adhesin proteins into the cell wall of C. parapsilosis is highly associated with colony morphology, which governs important clinical parameters such as biofilm formation capacity and at least partially alters drug susceptibility.