Biofilm as fungal adaptation strategy

Author: R. Rajendran

Author address:

University of Glasgow, Glasgow, United Kingdom

Full conference title:

8th Trends in Medical Mycology, Organised under the auspices of EORTC-IDG and ECMM, 6-9 October 2017, Belgrade, Serbia

Date: 16 October 2017

Abstract:

A biofilm is any group of microorganisms adhered to a surface and encased in a matrix of exopolymeric material, tolerant to antimicrobial agents. This is of particular significance since it is now estimated that a significant proportion of all human microbial infections involve biofilm formation. Fungal species are frequently found in the normal microbiota of humans, which facilitates their encounter with most implanted biomaterials and host surfaces. Candida and Aspergillus species are the predominant and well-known fungal pathogens found in the CF lung mycobiome. They are often co-isolated with bacterial species including Pseudomonas and Staphylococcus. Fungi form biofilms in response to different environmental cues. Biofilm formation by clinical isolates of Candida albicans is highly variable and is associated with poor clinical outcome. The mechanisms underpinning fungal biofilm heterogeneity remain unclear. We stratified C. albicans clinical isolates as high (HBF) or low (LBF) biofilm formers, and demonstrated that LBF phenotype could be induced into the HBF through the addition of clinically relevant stimuli such as serum or bacteria (Staphylococcus). Interestingly, HBF were unaffected. This suggests that some clinical isolates have stable biofilm production and others form biofilms in an adaptive manner. None of these isolates were found to be resistant to any of the antifungals tested. However, population analysis profiling found that HBF phenotype were heteroresistant to azole drug. We then investigated the mechanisms of biofilm heterogeneity by transcriptomics and metabolomics analysis. Using an unbiased computational approach we investigated the central metabolic pathways driving biofilm formation. With a dedicated computational pipeline, we found that amino acid metabolism such as arginine, serine and aspartate metabolism, were predominantly upregulated in the HBF phenotype. On the contrary, starch and sucrose metabolism was generally upregulated in the LBF phenotype. Secretome analysis further confirmed the upregulation of amino acid metabolism in HBF phenotype. Transferases such as aspartate aminotransferase and serine hydroxymethyl transferase are the key enzymes upregulated with Candida adaption to form biofilms. Up regulation of the later enzyme plays an important role in cellular one-carbon pathways, serves the specific metabolic needs of the organism. Pharmacological inhibition of these enzymes significantly reduces the isolates ability to form biofilm. Collectively, these findings provide evidence that adaptive biofilm phenotype is associated with differential regulation of metabolic pathways. Understanding and targeting such pathways, such as amino acid metabolism, is potentially useful for developing diagnostics and new antifungals to treat biofilm-based infections. 

Abstract Number: S06.2

Conference Year: 2017

Link Conference abstract: 

TIMM 8th (2017)

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