Abstract
BackgroundEmergence of Candida glabrata, which causes potential life-threatening invasive candidiasis, has been widely associated with high morbidity and mortality. In order to cause disease in vivo, a robust and highly efficient metabolic adaptation is crucial for the survival of this fungal pathogen in human host. In fact, reprogramming of the carbon metabolism is believed to be indispensable for phagocytosed C. glabrata within glucose deprivation condition during infection.MethodsIn this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches.ResultsCollectively, a total of 1482 transcripts (26.96%) and 242 proteins (24.69%) were significantly up- or down-regulated. Both transcriptome and proteome data revealed that the regulation of alternative carbon metabolism in C. glabrata resembled other fungal pathogens such as Candida albicans and Cryptococcus neoformans, with up-regulation of many proteins and transcripts from the glyoxylate cycle and gluconeogenesis, namely isocitrate lyase (ICL1), malate synthase (MLS1), phosphoenolpyruvate carboxykinase (PCK1) and fructose 1,6-biphosphatase (FBP1). In the absence of glucose, C. glabrata shifted its metabolism from glucose catabolism to anabolism of glucose intermediates from the available carbon source. This observation essentially suggests that the glyoxylate cycle and gluconeogenesis are potentially critical for the survival of phagocytosed C. glabrata within the glucose-deficient macrophages.ConclusionHere, we presented the first global metabolic responses of C. glabrata to alternative carbon source using transcriptomic and proteomic approaches. These findings implicated that reprogramming of the alternative carbon metabolism during glucose deprivation could enhance the survival and persistence of C. glabrata within the host.
Highlights
Candida glabrata, an opportunistic human pathogen has become one of the most common etiological agents of invasive candidiasis caused by non-Candida albicans Candida (NCAC) species [1,2,3]
It is evident that fungal metabolism, carbon metabolism is of primary importance to human fungal pathogens
We showed that C. glabrata mainly depended on the glyoxylate cycle and gluconeogenic growth to replenish glucose intermediates and generate energy from acetate
Summary
An opportunistic human pathogen has become one of the most common etiological agents of invasive candidiasis caused by non-Candida albicans Candida (NCAC) species [1,2,3]. Chew et al J Biomed Sci (2021) 28:1 the survival of pathogenic Candida species [4,5,6,7] These studies suggest that Candida species must be able to utilize a wide range of alternative carbon sources such as lactate and acetate within human host niches. Carbon metabolism affects multiple physiological, immunological and pathogenic attributes of Candida species in glucose-deficient condition [10,11,12]. We have demonstrated that alternative carbon sources induce physiological changes related to the pathogenicity of C. glabrata [13] These include changes in planktonic and biofilm growth, cell wall architecture, oxidative stress resistance and antifungal susceptibility. Reprogramming of the carbon metabolism is believed to be indispensable for phagocytosed C. glabrata within glucose deprivation condition during infection
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