Wertheimer Noa Blutraich, Stone Neil, Berman Judith
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Britannia 418, Ramat Aviv, Israel.
Institute of Infection and Immunity, St George's, University of London, London SW17 0RE, UK.
Philos Trans R Soc Lond B Biol Sci. 2016 Dec 5;371(1709). doi: 10.1098/rstb.2015.0461.
Rapid responses to acute stresses are essential for stress survival and are critical to the ability of fungal pathogens to adapt to new environments or hosts. The rapid emergence of drug resistance is used as a model for how fungi adapt and survive stress conditions that inhibit the growth of progenitor cells. Aneuploidy and loss of heterozygosity (LOH), which are large-scale genome shifts involving whole chromosomes or chromosome arms, occur at higher frequency than point mutations and have the potential to mediate stress survival. Furthermore, the stress of exposure to an antifungal drug can induce elevated levels of LOH and can promote the formation of aneuploids. This occurs via mitotic defects that first produce tetraploid progeny with extra spindles, followed by chromosome mis-segregation. Thus, drug exposure induces elevated levels of aneuploidy, which can alter the copy number of genes that improve survival in a given stress or drug. Selection then acts to increase the proportion of adaptive aneuploids in the population. Because aneuploidy is a common property of many pathogenic fungi, including those posing emerging threats to plants, animals and humans, we propose that aneuploid formation and LOH often accompanying it contribute to the rapid generation of diversity that can facilitate the emergence of fungal pathogens to new environmental niches and/or new hosts, as well as promote antifungal drug resistance that makes emerging fungal infections ever more difficult to contain.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.
对急性应激的快速反应对于应激生存至关重要，对真菌病原体适应新环境或宿主的能力也至关重要。耐药性的迅速出现被用作研究真菌如何适应和在抑制祖细胞生长的应激条件下生存的模型。非整倍体和杂合性缺失（LOH）是涉及整条染色体或染色体臂的大规模基因组变化，其发生频率高于点突变，并且有可能介导应激生存。此外，接触抗真菌药物的应激可诱导LOH水平升高，并可促进非整倍体的形成。这是通过有丝分裂缺陷发生的，该缺陷首先产生具有额外纺锤体的四倍体后代，随后是染色体错分离。因此，药物暴露会诱导非整倍体水平升高，这可能会改变在特定应激或药物中提高生存能力的基因拷贝数。然后选择作用于增加群体中适应性非整倍体的比例。由于非整倍体是许多致病真菌的共同特性，包括那些对植物、动物和人类构成新威胁的真菌，我们提出非整倍体的形成以及常常伴随的LOH有助于快速产生多样性，这可以促进真菌病原体向新的生态位和/或新宿主的出现，以及促进抗真菌药物耐药性，使新出现的真菌感染越来越难以控制。本文是主题为“应对真菌对动物健康、粮食安全和生态系统恢复力的新威胁”的特刊的一部分。
