Multi-omics Signature of Candida auris , an Emerging and Multidrug-Resistant Pathogen

Abstract

Candida auris is a recently described pathogenic fungus that is causing invasive outbreaks on all continents. The fungus is of high concern given the numbers of multidrug-resistant strains that have been isolated in distinct sites across the globe. The fact that its diagnosis is still problematic suggests that the spreading of the pathogen remains underestimated. Notably, the molecular mechanisms of virulence and antifungal resistance employed by this new species are largely unknown. In the present work, we compared two clinical isolates of C. auris with distinct drug susceptibility profiles and a Candida albicans reference strain using a multi-omics approach. Our results show that, despite the distinct drug resistance profile, both C. auris isolates appear to be very similar, albeit with a few notable differences. However, compared to C. albicans both C. auris isolates have major differences regarding their carbon utilization and downstream lipid and protein content, suggesting a multifactorial mechanism of drug resistance. The molecular profile displayed by C. auris helps to explain the antifungal resistance and virulence phenotypes of this new emerging pathogen. IMPORTANCE Candida auris was first described in Japan in 2009 and has now been the cause of significant outbreaks across the globe. The high number of isolates that are resistant to one or more antifungals, as well as the high mortality rates from patients with bloodstream infections, has attracted the attention of the medical mycology, infectious disease, and public health communities to this pathogenic fungus. In the current work, we performed a broad multi-omics approach on two clinical isolates isolated in New York, the most affected area in the United States and found that the omic profile of C. auris differs significantly from C. albicans. In addition to our insights into C. auris carbon utilization and lipid and protein content, we believe that the availability of these data will enhance our ability to combat this rapidly emerging pathogenic yeast.

Multiple Alternative Carbon Pathways Combine To Promote Candida albicans Stress Resistance, Immune Interactions, and Virulence

“…Gluconeogenic genes are also induced in vivo (21,57), and these transcriptional changes are often advantageous for microbial pathogens. Stress resistance induced in the presence of alternative carbon sources has been observed in other Candida species, including C. glabrata and the emerging pathogen C. auris (58,59), and numerous examples of beneficial effects of utilization of alternative carbon sources have been seen in bacterial pathogens. For example, Staphylococcus aureus, a facultative intracellular pathogen, alters its central carbon metabolism to promote its survival in the phagosome (60,61).…”

Nine Things Genomics Can Tell Us About Candida auris

“…S639P in FKS1 was recently shown to be the most widespread mutation associated with echinocandin resistance (Chow et al, 2020). A recent multi-omics analysis revealed that although the cell wall remodeling enzymes concentration was lower in C. auris when compared to C. albicans, in a drug-resistant C. auris isolate (MIC fluconazole: > 256 µg/mL, MIC caspofungin: 2 µg/mL) cell wall integrity proteins were upregulated, suggesting that the cell wall metabolism can be adjusted in response to drug treatment (Zamith-Miranda et al, 2019).…”

“…C. auris metabolism favors respiration as evidenced by enrichment in glycolytic and sugar transporter gene expression during yeast growth (Yue et al, 2018) and TCA cycle protein enrichment compared to C. albicans (Zamith-Miranda et al, 2019). Respiratory metabolism enhances ATP production and can reduce oxidative stress in C. albicans, thus promoting in vivo fitness and fluconazole resistance (Guo et al, 2017).…”

“…Respiratory metabolism enhances ATP production and can reduce oxidative stress in C. albicans, thus promoting in vivo fitness and fluconazole resistance (Guo et al, 2017). Furthermore, C. auris lipid profiles show elevated levels of ergosterol and structural lipids compared to C. albicans, which may influence stress and antifungal resistance (Zamith-Miranda et al, 2019).…”

Candida auris: A Decade of Understanding of an Enigmatic Pathogenic Yeast

“…Here, a number of important transcripts were differentially expressed, particularly adhesins IFF4 and CSA1, ALS-gene family members, and other biofilm related genes, such as secreted aspartyl protease and extra-cellular matrix related components. More recently, it has been reported through the use of multi-omics approaches that in comparison to C. albicans, C. auris exhibits significant differences in carbon utilisation and downstream cellular protein and lipid content [32]. It is likely that further pathogenic insights will begin to emerge as large scale data-sets are produced.…”