Comparative functional analysis of a new CDR1-like ABC transporter gene in multidrug resistance and virulence between Magnaporthe oryzae and Trichophyton mentagrophytes

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Abstract

Fungi are notorious for causing diseases in plants and domestic animals. ABC transporters play pivotal roles in multidrug resistance in fungi, with some ABC proteins indispensable for the pathogenicity of plant fungal pathongens. However, the roles of ABC proteins in animal pathogenic fungi, and the functional connections between ABC homologues in plant and animal pathogenic fungi are largely obscure. Here, we first functionally compared ABCG-1 proteins in rice-blast fungus Magnaporthe oryzae and identified MoCDR1 , a new ABC gene invovled in pathogencity. MoCDR1 disruption caused hypersensitivity to multidrugs, and impaired conidiation, appressorium formation and pathogenicity. Subsequently, we systematically retrieved ABC proteins in animal pathogenic fungus Trichophyton mentagrophytes and identified TmCdr1, a homologue to MoCdr1. TmCDR1 effectively rescued the drug sensitivity and virulece of Δ Mocdr1 , and mediated the drug resistance in T. mentagrophytes . TmCDR1 deletion did not significantly weaken the lesions on animal skin, but the mutant elicited a lower response on mouse macrophages than the wild type. Moreover, MoCdr1 and TmCdr1 are conserved in structures and functions, and both involved in drug resistance and pathogenicity by analogously regulating gene expression levels related to transporter activity, MAPK signaling pathway, and metabolic processes. Altogether, our results represents the first comprehensive characterization of ABC genes in T. mentagrophytes , establishing a functional correlation between homologous ABC genes in plant and animal pathogenic fungi.

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