Polak Iwona, Stryiński Robert, Paukszto Łukasz, Jastrzębski Jan Paweł, Bogacka Iwona, Łopieńska-Biernat Elżbieta
Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
Department of Botany and Evolutionary Ecology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
Front Cell Infect Microbiol. 2025 Aug 20;15:1621051. doi: 10.3389/fcimb.2025.1621051. eCollection 2025.
Glucose transporter (GLUT) research in parasitic nematodes focuses on identifying and characterizing developmentally regulated isoforms, elucidating their regulatory and structural properties, and evaluating their potential as drug targets. While glucose transport mechanisms have been well characterized in the free-living nematode , data on parasitic species remain limited. s. s., a parasitic nematode, relies on host-derived glucose to maintain energy metabolism. It is hypothesized that s. s. utilizes specific glucose transporters to facilitate sugar uptake under varying nutritional conditions.
analysis identified five putative facilitated glucose transporter genes () and one Sugars Will Eventually be Exported Transporter () gene. The FGTs were classified as members of the solute carrier family 2 (SLC2), while belonged to the SWEET transporter family. Full-length cDNA sequences were obtained, and encoded proteins structurally characterized using bioinformatic modeling. Expression of transporter genes was assessed in s. s. larvae at stages L3 and L4 cultured under different glucose concentrations and time points.
Structural and phylogenetic analyses revealed that and share high similarity with class I GLUTs found in nematodes and vertebrates. Gene expression profiling demonstrated differential regulation between larval stages. Most notably, FGT genes were stably expressed in L4 larvae, whereas in L3 larvae, gene activation was more variable and dependent on glucose concentration, showing a dynamic transcriptional response to nutrient levels. was expressed in both stages, but its regulation differed over time and with glucose availability. Glucose supplementation altered trehalose and glycogen levels, and trehalase activity varied across stages and treatments, indicating stage-specific metabolic adaptation.
The observed transcriptional and biochemical differences between L3 and L4 larvae suggest a shift in glucose uptake mechanisms, from transcuticular absorption in L3 to intestinal glucose uptake in L4 following intestine activation. FGT1 and FGT3 are proposed as key facilitators of glucose uptake, with roles varying across developmental stages. These findings indicate that glucose transporters are regulated in response to changing environmental conditions and may represent targets for rational anthelmintic drug design.
寄生线虫中葡萄糖转运蛋白（GLUT）的研究主要集中在识别和表征发育调控的异构体、阐明其调控和结构特性以及评估其作为药物靶点的潜力。虽然在自由生活线虫中葡萄糖转运机制已得到充分表征，但关于寄生线虫物种的数据仍然有限。粪类圆线虫（Strongyloides stercoralis，s.s.）是一种寄生线虫，依赖宿主来源的葡萄糖来维持能量代谢。据推测，粪类圆线虫利用特定的葡萄糖转运蛋白在不同营养条件下促进糖分摄取。
分析鉴定出五个推定的易化葡萄糖转运蛋白基因（FGTs）和一个糖最终输出转运蛋白（SWEET）基因。FGTs被归类为溶质载体家族2（SLC2）的成员，而SWEET属于SWEET转运蛋白家族。获得了全长cDNA序列，并使用生物信息学建模对编码蛋白进行了结构表征。在不同葡萄糖浓度和时间点培养的L3和L4期粪类圆线虫幼虫中评估了转运蛋白基因的表达。
结构和系统发育分析表明，FGTs和SWEET与线虫和脊椎动物中发现的I类GLUTs具有高度相似性。基因表达谱显示幼虫阶段之间存在差异调控。最值得注意的是，FGT基因在L4幼虫中稳定表达，而在L3幼虫中，基因激活更具变异性且依赖于葡萄糖浓度，显示出对营养水平的动态转录反应。SWEET在两个阶段均有表达，但其调控随时间和葡萄糖可用性而不同。补充葡萄糖改变了海藻糖和糖原水平，并且海藻糖酶活性在不同阶段和处理中有所变化，表明存在阶段特异性代谢适应。
在L3和L4幼虫之间观察到的转录和生化差异表明葡萄糖摄取机制发生了转变，从L3期的经皮吸收转变为L4期肠道激活后的肠道葡萄糖摄取。FGT1和FGT3被认为是葡萄糖摄取的关键促进因子，其作用在不同发育阶段有所不同。这些发现表明葡萄糖转运蛋白是根据不断变化的环境条件进行调控的，可能代表合理抗蠕虫药物设计的靶点。
