Functional Genomic and Biochemical Analysis Reveals Pleiotropic Effect of Congo Red on Aspergillus fumigatus.
Functional Genomic and Biochemical Analysis Reveals Pleiotropic Effect of Congo Red on Aspergillus fumigatus.
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DOI：
10.1128/mbio.00863-21
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发表时间：
2021-05-18
期刊：
影响因子：
6.4
通讯作者：
Latgé JP
中科院分区：
文献类型：
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作者：
Liu Z;Raj S;van Rhijn N;Fraczek M;Michel JP;Sismeiro O;Legendre R;Varet H;Fontaine T;Bromley M;Latgé JP
刚果红 (CR) 对真菌生长的抑制作用被认为与与 β-1,3-葡聚糖的特异性结合有关，β-1,3-葡聚糖可阻断细胞壁多糖的合成。在这项研究中，我们寻找调节 CR 反应的转录因子 (TF) 并探究它们的调节子。在研究TF突变体库对CR的敏感性过程中，发现并进一步研究了几种CR抗性和超敏感突变体。在 CR 存在的情况下，可以看到异常扭曲、肿胀的分生孢子，称为卡西莫多细胞。抗性突变体中的卡西莫多细胞比敏感菌株和亲本菌株中的细胞更大；因此，抗性突变体的分生孢子比敏感菌株或亲本菌株的萌发分生孢子吸收更多的CR。因此，卡西莫多细胞的较高吸收率导致 CR 从培养基中去除，从而允许一部分分生孢子发芽和生长。相反，敏感突变体和亲本菌株的所有休眠分生孢子均被杀死。这一结果表明，分生孢子群体的异质性对于促进烟曲霉在 CR 存在下的存活至关重要。此外，无定形表面细胞壁多糖（例如半乳糖氨基半乳聚糖）控制 CR 流入细胞内，从而控制药物耐药性。最后，与CR的长期培养导致发现了一种新的CR诱导生长效应，称为药物诱导生长刺激（DIGS），因为其中一个在从CR应激恢复后可以被刺激生长。
Inhibition of fungal growth by Congo red (CR) has been putatively associated with specific binding to β-1,3-glucans, which blocks cell wall polysaccharide synthesis. In this study, we searched for transcription factors (TFs) that regulate the response to CR and interrogated their regulon. During the investigation of the susceptibility to CR of the TF mutant library, several CR-resistant and -hypersensitive mutants were discovered and further studied. Abnormal distorted swollen conidia called Quasimodo cells were seen in the presence of CR. Quasimodo cells in the resistant mutants were larger than the ones in the sensitive and parental strains; consequently, the conidia of the resistant mutants absorbed more CR than the germinating conidia of the sensitive or parental strains. Accordingly, this higher absorption rate by Quasimodo cells resulted in the removal of CR from the culture medium, allowing a subset of conidia to germinate and grow. In contrast, all resting conidia of the sensitive mutants and the parental strain were killed. This result indicated that the heterogeneity of the conidial population is essential to promote the survival of Aspergillus fumigatus in the presence of CR. Moreover, amorphous surface cell wall polysaccharides such as galactosaminogalactan control the influx of CR inside the cells and, accordingly, resistance to the drug. Finally, long-term incubation with CR led to the discovery of a new CR-induced growth effect, called drug-induced growth stimulation (DIGS), since the growth of one of them could be stimulated after recovery from CR stress.