Investigating the Transcriptome of Candida albicans in a Dual-Species Staphylococcus aureus Biofilm Model

Abstract

<i>Candida albicans</i> is an opportunistic pathogen found throughout multiple body sites and is frequently co-isolated from infections of the respiratory tract and oral cavity with <i>Staphylococcus aureus.</i> Herein we present the first report of the effects that <i>S. aureus</i> elicits on the <i>C. albicans</i> transcriptome. Dual-species biofilms containing <i>S. aureus</i> and <i>C. albicans</i> mutants defective in <i>ALS3</i> or <i>ECE1</i> were optimised and characterised, followed by transcriptional profiling of <i>C. albicans</i> by RNA-sequencing (RNA-seq). Altered phenotypes in <i>C. albicans</i> mutants revealed specific interaction profiles between fungus and bacteria. The major adhesion and virulence proteins Als3 and Ece1, respectively, were found to have substantial effects on the <i>Candida</i> transcriptome in early and mature biofilms. Despite this, deletion of <i>ECE1</i> did not adversely affect biofilm formation or the ability of <i>S. aureus</i> to interact with <i>C. albicans</i> hyphae. Upregulated genes in dual-species biofilms corresponded to multiple gene ontology terms, including those attributed to virulence, biofilm formation and protein binding such as <i>ACE2</i> and multiple heat-shock protein genes. This shows that <i>S. aureus</i> pushes <i>C. albicans</i> towards a more virulent genotype, helping us to understand the driving forces behind the increased severity of <i>C. albicans</i>-<i>S. aureus</i> infections.