LITERATURE UPDATE
Single C. auris case reported
Transmissions or multiple cases of C. auris reported
US C. auris cases linked to healthcare stays in these countries
Global spread of Candida auris in 2019.
properties of C. auris isolates showed robust growth on intermediates of the tricarboxylic acid cycle, such as citrate and succinic and malic acids. However, there was reduced or no growth on pyruvate, lactic acid, or acetate, likely due to the lack of the monocarboxylic acid transporter Jen1, which is conserved in most pathogenic Candida species. Comparison of C. auris and C. albicans transcriptomes of cells grown on alternative carbon sources and dipeptides as a nitrogen source revealed common as well as species-unique responses. C. auris induced a significant number of genes with no orthologue in C. albicans (eg genes similar to the nicotinic acid transporter TNA1 [alternative carbon sources] and to the oligopeptide transporter [OPT] family [dipeptides]). Thus, C. auris possesses unique metabolic features which could have contributed to its emergence as a pathogen. Four main clades of the emerging multidrug-resistant human pathogen C. auris have been identified, and they differ in their susceptibilities to antifungals and disinfectants. Moreover, clade- and strain-specific metabolic differences have been identified, but a comprehensive overview of nutritional characteristics and resistance to various stressors is missing. Here, the authors performed high- throughput phenotypic characterisation of C. auris on various nutrients, stressors and chemicals, and obtained transcriptomes of cells grown on selected nutrients. The generated data sets identified multiple clade- and strain-specific phenotypes and induction of C. auris-specific metabolic genes, showing unique metabolic properties. The presented work provides a large amount of information for further investigations that could explain the role
of metabolism in the emergence and pathogenicity of this multidrug-resistant fungus.
Environmental reservoirs of the drug- resistant pathogenic yeast Candida auris Akinbobola AB, Kean R, Hanifi SMA, Quilliam RS. PLoS Pathog. 2023 Apr 13; 19 (4): e1011268. doi: 10.1371/journal. ppat.1011268. eCollection 2023 Apr.
Candia auris is an emerging human pathogenic yeast; yet, despite phenotypic attributes and genomic evidence suggesting that it probably emerged from a natural reservoir, nothing is known about the environmental phase of its life cycle and the transmission pathways associated with it. The thermotolerant characteristics
of C. auris have been hypothesised to be an environmental adaptation to increasing temperatures due to global warming (which may have facilitated its ability to tolerate the mammalian thermal barrier that is considered a protective strategy for humans against colonisation by environmental fungi with pathogenic potential). Thus, C. auris may be the first human pathogenic fungus to have emerged as a result of climate change. In addition, the release of antifungal chemicals, such as azoles, into the environment (from both pharmaceutical and agricultural sources) is likely to be responsible for the environmental enrichment of resistant strains of C. auris; however, the survival and dissemination of C. auris in the natural environment is poorly understood. In this paper, the authors critically
review the possible pathways through which C. auris can be introduced into the environment and evaluate the
WWW.PATHOLOGYINPRACTICE.COM FEBRUARY 2024
environmental characteristics that can influence its persistence and transmission in natural environments. Identifying potential environmental niches and reservoirs of C. auris and understanding its emergence against a backdrop of climate change and environmental pollution will be crucial for the development of effective epidemiological and environmental management responses.
Candida auris uses metabolic strategies to escape and kill macrophages while avoiding robust activation of the NLRP3 inflammasome response Weerasinghe H, Simm C, Djajawi TM et al. Cell Rep. 2023 May 30; 42 (5): 112522. doi: 10.1016/j.celrep.2023.112522.
Metabolic adaptations regulate the response of macrophages to infection. The contributions of metabolism to macrophage interactions with the emerging fungal pathogen Candida auris are poorly understood.
In this article, the authors show that
C. auris-infected macrophages undergo immunometabolic reprogramming and increase glycolysis but fail to activate a strong interleukin (IL)-1β cytokine response or curb C. auris growth. Further analysis shows that C. auris relies on its own metabolic capacity to escape from macrophages and proliferate in vivo. Furthermore, C. auris kills macrophages by triggering host metabolic stress through glucose starvation. However, despite causing macrophage cell death, C. auris does not trigger robust activation of the NLRP3 inflammasome. Consequently, inflammasome-dependent responses remain low throughout infection.
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