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.
METHODS: The probiotic characteristics of Ld45E were evaluated by examining its morphology, pH tolerance, adhesive ability onto HeLa cells, hemolytic activity, antibiotic susceptibility, and autoaggregation ability. Then, the antimicrobial activity of Ld45E was determined using Ld45E culture, cell-free supernatant, and crude bacteriocin solution. Co-aggregation and competition ability assays against various pathogens were conducted. The immunoregulatory effects of Ld45E were analyzed by measuring the proinflammatory cytokine IL-17. A p-value less than 0.05 was considered statistical significance.
RESULTS: Ld45E is 3-5 mm in diameter and round with a flat-shaped colony. pH 4 and 4.5 were the most favorable range for Ld45E growth within 12 h of incubation. Ld45E showed a strong adhesion ability onto HeLa cells (86%) and negative hemolytic activities. Ld45E was also sensitive to ceftriaxone, cefuroxime, ciprofloxacin, and doxycycline. We found that it had a good autoaggregation ability of 80%. Regarding antagonistic properties, Ld45E culture showed strong antimicrobial activity against GBS, E. coli, and Klebsiella spp. but only a moderate effect on C. parapsilosis. Cell-free supernatant of Ld45E exerted the most potent inhibitory effects at 40 °C against all genital pathogens, whereas bacteriocin showed a robust inhibition at 37 °C and 40 °C. The highest co-aggregation affinity was observed with GBS (81%) and E. coli (40%). Competition ability against the adhesion of GBS (80%), E. coli (76%), Klebsiella (72%), and C. parapsilosis (58%) was found. Ld45E was able to reduce the induction of the proinflammatory protein IL-17.
CONCLUSIONS: Ld45E possessed antimicrobial and immunoregulatory properties, with better cell-on-cell activity than supernatant activity. Thus, Ld45E is a potential probiotic candidate for adjunct therapy to address vaginal infections.
METHODS: The present pilot study investigated plasma protein profiles of leptospirosis patients and compared them against two control groups which consisted of dengue patients and healthy individuals. The plasma protein digests were analyzed using shotgun approach by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein abundances were estimated from the exponentially modified protein abundance index (emPAI) values. Plasma proteins in leptospirosis patients with at least two-fold differential expression compared to dengue and healthy control groups (p
METHODS: In this single-centre retrospective study, comparative analysis on clinical presentations and laboratory findings was performed between confirmed leptospirosis versus non-leptospirosis cases.
RESULTS: In multivariate logistic regression evidenced by a Hosmer-Lemeshow significance value of 0.979 and Nagelkerke R square of 0.426, the predictors of a leptospirosis case are hypocalcemia (calcium <2.10mmol/L), hypochloremia (chloride <98mmol/L), and eosinopenia (absolute eosinophil count <0.040×109/L). The proposed diagnostic scoring model has a discriminatory power with area under the curve (AUC) 0.761 (p<0.001). A score value of 6 reflected a sensitivity of 0.762, specificity of 0.655, a positive predictive value of 0.38, negative predictive value of 0.91, a positive likelihood ratios of 2.21, and a negative likelihood ratios of 0.36.
CONCLUSION: With further validation in clinical settings, implementation of this diagnostic scoring model is helpful to manage presumed leptospirosis especially in the absence of leptospirosis confirmatory tests.
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.