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Published on: October 20, 2020
Proteomic profile of Cryptococcus neoformans biofilm reveals changes in metabolic processes
Lucélia Santi1, Walter O Beys-da-Silva, Markus Berger
1Department of Chemical Physiology, The Scripps Research Institute , North Torrey Pines Road, Suite 11, La Jolla, California 92037, United States.
Abstract:
Cryptococcus neoformans, a pathogenic yeast, causes meningoencephalitis, especially in immunocompromised patients, leading in some cases to death. Microbes in biofilms can cause persistent infections, which are harder to treat. Cryptococcal biofilms are becoming common due to the growing use of brain valves and other medical devices. Using shotgun proteomics we determine the differences in protein abundance between biofilm and planktonic cells. Applying bioinformatic tools, we also evaluated the metabolic pathways involved in biofilm maintenance and protein interactions. Our proteomic data suggest general changes in metabolism, protein turnover, and global stress responses. Biofilm cells show an increase in proteins related to oxidation-reduction, proteolysis, and response to stress and a reduction in proteins related to metabolic process, transport, and translation. An increase in pyruvate-utilizing enzymes was detected, suggesting a shift from the TCA cycle to fermentation-derived energy acquisition. Additionally, we assign putative roles to 33 proteins previously categorized as hypothetical. Many changes in metabolic enzymes were identified in studies of bacterial biofilm, potentially revealing a conserved strategy in biofilm lifestyle.
Insights
Cryptococcus neoformans biofilms, often found on medical devices, exhibit altered protein levels. Biofilm cells prioritize stress response and fermentation over metabolism and translation, suggesting conserved microbial strategies.
Area of Science:
- Mycology
- Microbial Pathogenesis
- Proteomics
Background:
- Cryptococcus neoformans is a yeast causing life-threatening meningoencephalitis, particularly in immunocompromised individuals.
- Microbial biofilms are implicated in persistent, difficult-to-treat infections, with increasing prevalence linked to medical devices like brain valves.
- Understanding the molecular differences between planktonic and biofilm states of C. neoformans is crucial for developing targeted therapies.
Purpose of the Study:
- To compare protein abundance between Cryptococcus neoformans biofilm and planktonic cells using shotgun proteomics.
- To identify metabolic pathways and protein interactions involved in biofilm maintenance.
- To assign functions to hypothetical proteins within the C. neoformans biofilm.
Main Methods:
- Shotgun proteomics was employed to quantify protein expression differences.
- Bioinformatic analyses were used to evaluate metabolic pathways and protein-protein interactions.
- Comparative analysis between biofilm and planktonic cell proteomes was performed.
Main Results:
- Significant alterations in protein abundance were observed, including increased proteins involved in oxidation-reduction, proteolysis, and stress response.
- A decrease in proteins related to metabolic processes, transport, and translation was noted in biofilm cells.
- Increased pyruvate-utilizing enzymes suggest a metabolic shift from the TCA cycle towards fermentation for energy.
- Putative functions were assigned to 33 previously hypothetical proteins.
Conclusions:
- Cryptococcal biofilm formation involves widespread metabolic reprogramming and enhanced stress responses.
- The observed metabolic and protein turnover changes in C. neoformans biofilms may represent a conserved strategy across microbial biofilm lifestyles.
- These findings provide insights into the molecular mechanisms of cryptococcal biofilm persistence and potential therapeutic targets.
