原虫持久细胞与药物治疗失败。
Protozoan persister-like cells and drug treatment failure.
机构信息
Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA.
出版信息
Nat Rev Microbiol. 2019 Oct;17(10):607-620. doi: 10.1038/s41579-019-0238-x. Epub 2019 Aug 23.
Abstract
Antimicrobial treatment failure threatens our ability to control infections. In addition to antimicrobial resistance, treatment failures are increasingly understood to derive from cells that survive drug treatment without selection of genetically heritable mutations. Parasitic protozoa, such as Plasmodium species that cause malaria, Toxoplasma gondii and kinetoplastid protozoa, including Trypanosoma cruzi and Leishmania spp., cause millions of deaths globally. These organisms can evolve drug resistance and they also exhibit phenotypic diversity, including the formation of quiescent or dormant forms that contribute to the establishment of long-term infections that are refractory to drug treatment, which we refer to as 'persister-like cells'. In this Review, we discuss protozoan persister-like cells that have been linked to persistent infections and discuss their impact on therapeutic outcomes following drug treatment.
摘要
抗菌治疗失败威胁着我们控制感染的能力。除了抗菌药物耐药性之外，治疗失败越来越被认为是由于细胞在没有选择遗传突变的情况下存活下来导致的。寄生虫原生动物，如引起疟疾的疟原虫、刚地弓形虫和动基体原生动物，包括克氏锥虫和利什曼原虫等，在全球范围内导致数百万人死亡。这些生物体可以进化出耐药性，并且它们还表现出表型多样性，包括形成静止或休眠形式，有助于建立对药物治疗产生抗药性的长期感染，我们称之为“类持久细胞”。在这篇综述中，我们讨论了与持续性感染相关的原生动物类持久细胞，并讨论了它们对药物治疗后治疗结果的影响。
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2
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3
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PLoS Negl Trop Dis. 2019 Feb 4;13(2):e0007052. doi: 10.1371/journal.pntd.0007052. eCollection 2019 Feb.
4
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6
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