Ray Atrayee, Sarkar Srimonti
a Department of Biochemistry , Bose Institute , Kolkata , West Bengal , India.
Crit Rev Microbiol. 2017 Aug;43(4):481-492. doi: 10.1080/1040841X.2016.1262814. Epub 2016 Dec 30.
Giardia lamblia is the causative agent of the diarrheal disease giardiasis, against which only a limited number of drugs are currently available. Increasing reports of resistance to these drugs makes it necessary to identify new cellular targets for designing the next generation of anti-giardial drugs. Towards this goal, therapeutic agents that target the parasitic cellular machinery involved in the functioning of the unique microtubule-based cytoskeleton of the Giardia trophozoites are likely to be effective as microtubule function is not only important for the survival of trophozoites within the host, but also their extensive remodeling is necessary during the transition from trophozoites to cysts. Thus, drugs that affect microtubule remodeling have the potential to not only kill the disease-causing trophozoites, but also inhibit transmission of cysts in the community. Recent studies in other model organisms have indicated that the proteasome plays an integral role in the formation and remodeling of the microtubule-based cytoskeleton. This review draws attention to the various processes by which the giardial proteasome may impact the functioning of its microtubule cytoskeleton and highlights the possible differences of the parasitic proteasome and some of other cellular machinery involved in microtubule remodeling, compared to that of the higher eukaryotic host.
贾第虫是腹泻病贾第虫病的病原体，目前针对该病的可用药物数量有限。对这些药物耐药性的报道日益增多，因此有必要确定新的细胞靶点，以设计新一代抗贾第虫药物。为实现这一目标，靶向参与贾第虫滋养体独特微管细胞骨架功能的寄生细胞机制的治疗药物可能会有效，因为微管功能不仅对滋养体在宿主体内的存活很重要，而且在从滋养体向包囊转变过程中，其广泛重塑也是必要的。因此，影响微管重塑的药物不仅有可能杀死致病的滋养体，还能抑制包囊在群体中的传播。最近在其他模式生物中的研究表明，蛋白酶体在基于微管的细胞骨架的形成和重塑中起着不可或缺的作用。本综述关注贾第虫蛋白酶体可能影响其微管细胞骨架功能的各种过程，并强调了寄生蛋白酶体与参与微管重塑的其他一些细胞机制相比，与高等真核宿主的可能差异。
