Candida Albicans Cell Wall Integrity Transcription Factors Regulate Polymicrobial Biofilm Formation with Streptococcus Gordonii.

Polymicrobial biofilms play important roles in oral and systemic infections. The oral plaque bacteriumStreptococcus gordoniiis known to attach to the hyphal cell wall of the fungusCandida albicansto form corn-cob like structures in biofilms. However, the role ofC. albicansin formation of polymicrobial biofilms is not completely understood. The objective of this study was to determine the role ofC. albicanstranscription factors in regulation of polymicrobial biofilms and antibiotic tolerance ofS. gordonii. The proteins secreted byC. albicansandS. gordoniiin mixed planktonic cultures were determined using mass spectrometry. Antibiotic tolerance ofS. gordoniito ampicillin and erythromycin was determined in mixed cultures and mixed biofilms withC. albicans. Additionally, biofilm formation ofS. gordoniiwithC. albicansknock-out mutants of 45 transcription factors that affect cell wall integrity, filamentous growth and biofilm formation was determined. Furthermore, these mutants were also screened for antibiotic tolerance in mixed biofilms withS. gordonii. Analysis of secreted proteomes resulted in the identification of proteins being secreted exclusively in mixed cultures. Antibiotic testing showed thatS. gordoniihad significantly increased survival in mixed planktonic cultures with antibiotics as compared to single cultures.C. albicansmutants of transcription factors Sfl2, Brg1, Leu3, Cas5, Cta4, Tec1, Tup1, Rim101 and Efg1 were significantly affected in mixed biofilm formation. Also mixed biofilms ofS. gordoniiwith mutants ofC. albicanstranscription factors, Tec1 and Sfl2, had significantly reduced antibiotic tolerance as compared to control cultures. Our data indicates thatC. albicansmay have an important role in mixed biofilm formation as well as antibiotic tolerance ofS. gordoniiin polymicrobial biofilms.C. albicansmay play a facilitating role than being just an innocent bystander in oral biofilms and infections.