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Background  Emergence 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.    Methods  In this study, the metabolic responses of  C. glabrata  under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches.    Results  Collectively, 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.    Conclusion  Here, 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.

Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata