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Principal Investigator: Xiaorong Lin
Organization: UNIVERSITY OF GEORGIA
Fiscal Year: 2024
Award: $188,750
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
The objectives of this exploratory R21 proposal are to identify and characterize an intercellular communication
signal that induces biofilm formation in cooperation with quorum sensing in the human fungal pathogen
Cryptococcus neoformans. C. neoformans is a basidiomycetous fungus that causes cryptococcal
meningoencephalitis (CME), one of the most fatal and common opportunistic infections affecting people with
HIV/AIDS. Like many other infectious microbes, C. neoformans forms biofilm-like structures known as
cryptococcoma in vivo. However, we know very little about the structural requirements for biofilms or their
genetic regulation in this fungal pathogen, partly because Cryptococcus forms biofilms poorly under laboratory
conditions, and partly because this basidiomycete does not carry homologues of any known biofilm-relevant
proteins established in ascomycetes like Saccharomyces and Candida species.
Here we found that disruption of a transcription repressor Ssn6 in a mating-type a strain, but not in the
congenic mating-type α strain, leads to robust biofilm formation in C. neoformans, which provides an entry
point for us to investigate genetic regulation of biofilm formation in this fungus. Interestingly, ssn6a biofilm
colonies induce the nearby ssn6α colonies to also form biofilms and this process is independent of the mating
pheromone. We discovered that the intercellular communication system which activates biofilm formation
requires the quorum-sensing molecule Qsp1 and an unknown peptide-based signaling molecule. Here we
propose to (1) identify the secreted biofilm signaling molecule and (2) elucidate the pathway involved in biofilm
formation activated by this signaling molecule. The proposed work is expected to yield insights into this layered
communication system that regulates such complex community behaviors in a clinically important fungal
pathogen. We also expect to identify novel biofilm structural proteins like adhesins in Cryptococcus in this
process, which will fill the critical gap in our knowledge about biofilm formation and regulation in
basidiomycetes. The findings from this exploratory research will also provide a foundation for future
investigation of the impact of biofilm regulation on cryptococcal pathogenesis.
Terms: <3,7,11-trimethyl-2,6,10-dodecatrien-1-ol><AIDS/HIV><Adhesions><Affect><Ascomycetes><Ascomycota><Bacterial Adhesins><Basal Transcription Factor><Basal transcription factor genes><Basidiomycetes><Basidiomycota><Behavior><C neoformans><C. neoformans><Candida><Cell Communication and Signaling><Cell Signaling><Cell surface><Cell to Cell Communication and Signaling><Cell-Cell Signaling><Cerebromeningitis><Clinical><Communicable Diseases><Communication><Communities><Complex><Coupling><Cryptococcus><Cryptococcus neoformans><Encephalomeningitis><Environment><FPLC><Farnesol><Foundations><Future><Gene Deletion><Gene Expression><Gene Targeting><GeneHomolog><General Transcription Factor Gene><General Transcription Factors><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic defect><Genetics-Mutagenesis><Goals><HIV/AIDS><Homolog><Homologous Gene><Homologue><Human><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Intercellular Communication Process><Intracellular Communication and Signaling><Investigation><Knowledge><Laboratories><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Mating Types><Meningoencephalitis><Microbe><Microbial Biofilms><Microbiology><Modeling><Modern Man><Monilia><Mutagenesis><Mutagenesis Molecular Biology><Mutation><Nature><Opportunistic Infections><Partner in relationship><Pathogenesis><Pathway interactions><Peptides><Persons><Pheromone><Prevalence><Process><Production><Proteins><Public Health><Regulation><Research><Role><Saccharomyces><Signal Induction><Signal Transduction><Signal Transduction Systems><Signaling><Signaling Factor Proto-Oncogene><Signaling Molecule><Signaling Pathway Gene><Signaling Protein><Specificity><Structural Protein><Structure><System><T-DNA><TM Pharmacia Fast Protein Liquid Chromatography><Torula><Transcription Factor Proto-Oncogene><Transcription Repressor><Transcription factor genes><Transcriptional Repressor><Work><adhesin><biofilm><biological signal transduction><community microbes><congenic><discover genes><fast protein liquid chromatography><fungal pathogen><fungi pathogen><fungus><gene deletion mutation><gene discovery><genetic repressor><genome mutation><global gene expression><global transcription profile><in vivo><insight><intercellular communication><mate><microbial community><mutant><novel><overexpress><overexpression><pathogenic fungus><pathway><polymicrobial community><prevent><preventing><quorum sensing><response><sac fungi><social role><transcription factor><transcriptome>