Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
J Biomed Sci. 2019 Jul 13;26(1):52. doi: 10.1186/s12929-019-0546-5.
Carbon utilization and metabolism are fundamental to every living organism for cellular growth. For intracellular human fungal pathogens such as Candida glabrata, an effective metabolic adaptation strategy is often required for survival and pathogenesis. As one of the host defence strategies to combat invading pathogens, phagocytes such as macrophages constantly impose restrictions on pathogens' access to their preferred carbon source, glucose. Surprisingly, it has been reported that engulfed C. glabrata are able to survive in this harsh microenvironment, further suggesting alternative carbon metabolism as a potential strategy for this opportunistic fungal pathogen to persist in the host.
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.
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.
碳的利用和代谢是每个生物体进行细胞生长的基础。对于细胞内的人类真菌病原体,如光滑念珠菌,生存和发病机制通常需要有效的代谢适应策略。作为宿主防御策略之一,吞噬细胞(如巨噬细胞)不断限制病原体获取其首选碳源葡萄糖的机会。令人惊讶的是,据报道,被吞噬的光滑念珠菌能够在这种恶劣的微环境中存活,这进一步表明替代碳代谢可能是这种机会性真菌病原体在宿主中持续存在的一种潜在策略。
在这篇综述中,我们讨论了替代碳代谢作为光滑念珠菌发病机制的一种代谢适应策略。由于乙醛酸循环是利用替代碳源的重要途径,我们还强调了乙醛酸循环中的关键代谢酶及其对光滑念珠菌发病机制的必要性。最后,我们探讨了乙醛酸循环的转录调控网络。
鉴于白色念珠菌和酿酒酵母的证据,本综述总结了乙醛酸循环作为光滑念珠菌替代碳代谢途径的现有知识。