Herbicide glyphosate efficiently inhibits growth of pathogenic Prototheca algae species, suggesting the presence of novel pathways for the development of anti-algal drugs.
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引用次数: 0
Abstract
Prototheca are ubiquitous algae and occasional pathogens of humans and animals. While rare, the infection is often fatal and treatment options are limited to antifungals with low efficiency. Here, using growth curve assays, we demonstrate that five pathogenic species of Prototheca (P. blaschkeae, P. wickerhamii, P. cutis, P. ciferrii, P. bovis) were fully inhibited by 50-100 μg/mL of herbicide glyphosate, suggesting novel pathways that can be considered for anti-algal drug development.IMPORTANCEPrototheca are algae frequently found in the environment that occasionally cause infections in humans and animals. Although these infections are rare, they are often deadly for immunocompromised patients. Considering the rising ambient temperatures that promote algal bloom and a growing number of immunocompromised patients globally, such cases are likely to increase and will require efficient medications. Currently, the treatment is limited to antifungals that affect algal and animal membranes alike at concentrations close to toxic. Here, we hypothesized that targeting a pathway that is present in plants but not animals may be a new approach to the development of novel anti-algal compounds with high efficiency and lower toxicity. In this proof-of-principle study, we found that herbicide glyphosate, which targets the shikimate pathway found in plants but not in animals, efficiently inhibits all five tested pathogenic Prototheca, suggesting that the shikimate pathway may be a promising target for anti-algal drug development.
原生藻是一种普遍存在的藻类,也是人类和动物的偶然病原体。虽然罕见,但这种感染往往是致命的,治疗选择仅限于效率较低的抗真菌药物。通过生长曲线分析,我们发现5种致病性原藻(P. blaschkeae, P. wickerhamii, P. cutis, P. ciferrii, P. bovis)被50-100 μg/mL草甘膦完全抑制,提示可以考虑开发抗藻药物的新途径。原鞘是一种经常在环境中发现的藻类,偶尔会引起人类和动物的感染。虽然这些感染很罕见,但对于免疫功能低下的患者来说,它们往往是致命的。考虑到不断上升的环境温度会促进藻类繁殖,全球免疫功能低下的患者数量也在不断增加,这类病例可能会增加,需要有效的药物治疗。目前,这种治疗仅限于影响藻类和动物膜的抗真菌药物,浓度接近毒性。在这里,我们假设靶向存在于植物而不存在于动物的途径可能是开发高效低毒的新型抗藻化合物的新途径。在这项原理验证研究中,我们发现除草剂草甘膦,其靶向植物中发现的而不是动物中的莽草酸途径,有效地抑制了所有五种测试的致病性原藻,这表明莽草酸途径可能是抗藻药物开发的有希望的靶点。
期刊介绍:
Microbiology Spectrum publishes commissioned review articles on topics in microbiology representing ten content areas: Archaea; Food Microbiology; Bacterial Genetics, Cell Biology, and Physiology; Clinical Microbiology; Environmental Microbiology and Ecology; Eukaryotic Microbes; Genomics, Computational, and Synthetic Microbiology; Immunology; Pathogenesis; and Virology. Reviews are interrelated, with each review linking to other related content. A large board of Microbiology Spectrum editors aids in the development of topics for potential reviews and in the identification of an editor, or editors, who shepherd each collection.