Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Mexico.
Front Cell Infect Microbiol. 2022 Sep 23;12:976924. doi: 10.3389/fcimb.2022.976924. eCollection 2022.
The cell wall (CW) of fungi exhibits a complex structure and a characteristic chemical composition consisting almost entirely of interacting crystalline and amorphous polysaccharides. These are synthesized by a number of sugar polymerases and depolymerases encoded by a high proportion of the fungal genome (for instance, 20% in ). These enzymes act in an exquisitely coordinated process to assemble the tridimensional and the functional structure of the wall. Apart from playing a critical role in morphogenesis, cell protection, viability and pathogenesis, the CW represents a potential target for antifungals as most of its constituents do not exist in humans. Chitin, β-glucans and cellulose are the most frequent crystalline polymers found in the fungal CW. The hexosamine biosynthesis pathway (HBP) is critical for CW elaboration. Also known as the Leloir pathway, this pathway ends with the formation of UDP-N-GlcNAc after four enzymatic steps that start with fructose-6-phosphate and L-glutamine in a short deviation of glycolysis. This activated aminosugar is used for the synthesis of a large variety of biomacromolecules in a vast number of organisms including bacteria, fungi, insects, crustaceans and mammalian cells. The first reaction of the HBP is catalyzed by GlcN-6-P synthase (L-glutamine:D-fructose-6-phosphate amidotransferase; EC 2.6.1.16), a critical enzyme that has been considered as a potential target for antifungals. The enzyme regulates the amount of cell UDP-N-GlcNAc and in eukaryotes is feedback inhibited by the activated aminosugar and other factors. The native and recombinant forms of GlcN-6-P synthase has been purified and characterized from both prokaryotic and eukaryotic organisms and demonstrated its critical role in CW remodeling and morphogenesis after exposure of some fungi to agents that stress the cell surface by interacting with wall polymers. This review deals with some of the cell compensatory responses of fungi to wall damage induced by Congo Red and Calcofluor White.
真菌细胞壁(CW)具有复杂的结构和特征性的化学成分,几乎完全由相互作用的结晶和无定形多糖组成。这些多糖由许多糖聚合酶和解聚酶合成,这些酶由真菌基因组的很大一部分编码(例如, 在 中占 20%)。这些酶在一个极其协调的过程中发挥作用,组装细胞壁的三维和功能结构。除了在形态发生、细胞保护、活力和发病机制中发挥关键作用外,CW 还是抗真菌药物的潜在靶标,因为其大部分成分在人类中不存在。几丁质、β-葡聚糖和纤维素是真菌 CW 中最常见的结晶聚合物。己糖胺生物合成途径(HBP)对 CW 的形成至关重要。该途径也称为 Leloir 途径,在从果糖-6-磷酸和 L-谷氨酰胺开始的四个酶促步骤之后,以 UDP-N-GlcNAc 的形式结束,该途径在糖酵解的一个短暂偏离中进行。这种活化的氨基糖被用于包括细菌、真菌、昆虫、甲壳类动物和哺乳动物细胞在内的大量生物体中合成各种生物大分子。HBP 的第一个反应由 GlcN-6-P 合酶(L-谷氨酰胺:D-果糖-6-磷酸酰胺转移酶;EC 2.6.1.16)催化,该酶是一种关键酶,已被认为是抗真菌药物的潜在靶标。该酶调节细胞 UDP-N-GlcNAc 的量,在真核生物中,被活化的氨基糖和其他因素反馈抑制。GlcN-6-P 合酶的天然和重组形式已从原核和真核生物中纯化和表征,并证明其在某些真菌暴露于通过与细胞壁聚合物相互作用来胁迫细胞表面的试剂后,在 CW 重塑和形态发生中发挥关键作用。本文综述了真菌对刚果红和 Calcofluor White 诱导的细胞壁损伤的一些细胞补偿反应。