Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins.
Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins.
复制标题
通过靶向磷脂酰肌醇转移蛋白对抗真菌感染的新前景。
DOI：
10.3390/ijms22136754
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发表时间：
2021-06-23
影响因子：
5.6
通讯作者：
Bankaitis VA
中科院分区：
文献类型：
--
作者：
Khan D;Nile AH;Tripathi A;Bankaitis VA
对临床医生可用的有限的抗真菌剂具有抗性的真菌“超级细菌”的出现正在侵蚀我们有效治疗这些致命病原体感染的能力。随着真菌感染的威胁在全球范围内不断升级，这种不断减少的应对能力加剧了对即将发生的全球卫生紧急情况的担忧。这些发展强调了对新型抗真菌药物的迫切需求，因此，需要确定新的靶点。磷酸肌醇信号并没有立即出现提供有吸引力的目标，由于其在真核生物的进化保守。然而，最近的证据表明，情况并非如此。在这里，我们讨论的证据，确定Sec14样磷脂酰肌醇转移蛋白（PITP）作为未开发的门户网站，通过该门户网站，在有毒真菌中的磷酸肌醇信号可以被化学破坏与精致的选择性。最近鉴定出靶向真菌Sec14蛋白的先导化合物，这些化合物来自几种不同的化学支架，揭示了下一代Sec14抑制剂的合理设计的令人兴奋的进展。适当改进的下一代Sec14定向抑制剂的开发有望扩大可用于部署在真菌病原体及其人类宿主之间不断变化的领域中的化学武器。
The emergence of fungal “superbugs” resistant to the limited cohort of anti-fungal agents available to clinicians is eroding our ability to effectively treat infections by these virulent pathogens. As the threat of fungal infection is escalating worldwide, this dwindling response capacity is fueling concerns of impending global health emergencies. These developments underscore the urgent need for new classes of anti-fungal drugs and, therefore, the identification of new targets. Phosphoinositide signaling does not immediately appear to offer attractive targets due to its evolutionary conservation across the Eukaryota. However, recent evidence argues otherwise. Herein, we discuss the evidence identifying Sec14-like phosphatidylinositol transfer proteins (PITPs) as unexplored portals through which phosphoinositide signaling in virulent fungi can be chemically disrupted with exquisite selectivity. Recent identification of lead compounds that target fungal Sec14 proteins, derived from several distinct chemical scaffolds, reveals exciting inroads into the rational design of next generation Sec14 inhibitors. Development of appropriately refined next generation Sec14-directed inhibitors promises to expand the chemical weaponry available for deployment in the shifting field of engagement between fungal pathogens and their human hosts.
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影响因子：
3.7
作者：
Charlier C;Dromer F;Lévêque C;Chartier L;Cordoliani YS;Fontanet A;Launay O;Lortholary O;French Cryptococcosis Study Group
通讯作者：
French Cryptococcosis Study Group
影响因子：
11.4
作者：
Benli, M;Doring, F;Gallwitz, D
通讯作者：
Gallwitz, D
影响因子：
64.8
作者：
BANKAITIS, VA;AITKEN, JR;DOWHAN, W
通讯作者：
DOWHAN, W
DOI：
10.1083/jcb.108.4.1271
发表时间：
1989-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bankaitis VA;Malehorn DE;Emr SD;Greene R
通讯作者：
Greene R
对囊性纤维化中曲霉菌病不同表现的多国评估。
影响因子：
3.7
作者：
Armstead J;Morris J;Denning DW
通讯作者：
Denning DW