MAIN TEXT: In this review, we discuss alternative carbon metabolism as a metabolic adaptation strategy for the pathogenesis of C. glabrata. As the glyoxylate cycle is an important pathway in the utilization of alternative carbon sources, we also highlight the key metabolic enzymes in the glyoxylate cycle and its necessity for the pathogenesis of C. glabrata. Finally, we explore the transcriptional regulatory network of the glyoxylate cycle.
CONCLUSION: Considering evidence from Candida albicans and Saccharomyces cerevisiae, this review summarizes the current knowledge of the glyoxylate cycle as an alternative carbon metabolic pathway of C. glabrata.
DESIGN AND SETTING: We performed a retrospective review of medical records among emergency departments (EDs) of eight PATOS centres, from September 2014 - August 2015.
PARTICIPANTS: We included children <16 years old who presented within 24 hours of head injury and were admitted for observation or required a computed tomography (CT) of the brain from the ED. We excluded children with known coagulopathies, neurological co-morbidities or prior neurosurgery. We reviewed the mechanism, intent, location and object involved in each injury, and the patients' physical findings on presentation.
OUTCOMES: Primary outcomes were death, endotracheal intubation or neurosurgical intervention. Secondary outcomes included hospital and ED length of stay.
RESULTS: 1438 children were analysed. 953 children (66.3%) were male and the median age was 5.0 years (IQR 1.0-10.0). Falls predominated especially among children younger than 2 years (82.9%), while road traffic injuries were more likely to occur among children 2 years and above compared with younger children (25.8% vs 11.1%). Centres from upper and lower middle-income countries were more likely to receive head injured children from road traffic collisions compared with those from high-income countries (51.4% and 40.9%, vs 10.9%, p<0.0001) and attended to a greater proportion of children with severe outcomes (58.2% and 28.4%, vs 3.6%, p<0.0001). After adjusting for age, gender, intent of injury and gross national income, traffic injuries (adjusted OR 2.183, 95% CI 1.448 to 3.293) were associated with severe outcomes, as compared with falls.
CONCLUSIONS: Among children with head injuries, traffic injuries are independently associated with death, endotracheal intubation and neurosurgery. This collaboration among Asian centres holds potential for future prospective childhood injury surveillance.
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.