Szalewski David A, Hinrichs Victoria S, Zinniel Denise K, Barletta Raúl G
a Department of Biological Systems Engineering, University of Nebraska, Lincoln, NE 68583-0726, USA.
d Department of Microbiology, University of Nebraska, Lincoln, NE 68588-0664, USA.
Can J Microbiol. 2018 Jul;64(7):439-453. doi: 10.1139/cjm-2017-0749. Epub 2018 Mar 27.
The genus Aspergillus includes fungal species that cause major health issues of significant economic importance. These microorganisms are also the culprit for production of carcinogenic aflatoxins in grain storages, contaminating crops, and economically straining the production process. Aspergillus fumigatus is a very important pathogenic species, being responsible for high human morbidity and mortality on a global basis. The prevalence of these infections in immunosuppressed individuals is on the rise, and physicians struggle with the diagnosis of these deadly pathogens. Several virulence determinants facilitate fungal invasion and evasion of the host immune response. Metabolic functions are also important for virulence and drug resistance, since they allow fungi to obtain nutrients for their own survival and growth. Following a positive diagnostic identification, mortality rates remain high due, in part, to emerging resistance to frequently used antifungal drugs. In this review, we discuss the role of the main virulence, drug target, and drug resistance determinants. We conclude with the review of new technologies being developed to treat aspergillosis. In particular, microsphere and nanoparticle delivery systems are discussed in the context of improving drug bioavailability. Aspergillus will likely continue to cause problematic infections in immunocompromised patients, so it is imperative to improve treatment options.
曲霉属包括一些会引发具有重大经济意义的主要健康问题的真菌物种。这些微生物也是谷物储存中产生致癌黄曲霉毒素、污染农作物以及给生产过程造成经济负担的罪魁祸首。烟曲霉是一种非常重要的致病物种，在全球范围内导致了较高的人类发病率和死亡率。这些感染在免疫抑制个体中的患病率正在上升，医生们在诊断这些致命病原体时面临困难。几种毒力决定因素促进了真菌的侵袭以及对宿主免疫反应的逃避。代谢功能对毒力和耐药性也很重要，因为它们使真菌能够获取自身生存和生长所需的营养物质。在诊断明确后，死亡率仍然很高，部分原因是对常用抗真菌药物出现了耐药性。在本综述中，我们讨论了主要毒力、药物靶点和耐药性决定因素的作用。我们以对正在开发的治疗曲霉病的新技术的综述作为结尾。特别是，在提高药物生物利用度的背景下讨论了微球和纳米颗粒递送系统。曲霉很可能会继续在免疫功能低下的患者中引发问题感染，因此改善治疗选择势在必行。
