Functional characterization of genes encoding cadmium pumping P 1B -type ATPases in Aspergillus fumigatus and Aspergillus nidulans

Author:

Vig Ildikó12,Benkő Zsigmond1,Gila Barnabás Cs.1,Palczert Zoltán1,Jakab Ágnes3,Nagy Fruzsina3,Miskei Márton2,Lee Mi-Kyung4,Yu Jae-Hyuk5ORCID,Pócsi István12,Emri Tamás12ORCID

Affiliation:

1. Department of Molecular Biotechnology and Microbiology, Faculty of Sciences and Technology, University of Debrecen , Debrecen, Hungary

2. ELRN-UD Fungal Stress Biology Research Group , Debrecen, Hungary

3. Department of Medical Microbiology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary

4. Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology , Jeongeup-si, South Korea

5. Department of Bacteriology, University of Wisconsin-Madison , Madison, Wisconsin, USA

Abstract

ABSTRACT Several P 1B -type ATPases are important Cd 2+ /Cu 2+ pumps in Aspergillus species, and they are tightly associated with the heavy metal stress tolerance of these ascomycetous fungi. To better understand the roles of the two P 1B -type ATPases, Aspergillus nidulans CrpA Cd 2+ /Cu 2+ pump (orthologue of the Candida albicans Crp1 Cd 2+ /Cu 2+ pump) and Aspergillus fumigatus PcaA Cd 2+ pump (orthologue of the Saccharomyces cerevisiae Pca1 Cd 2+ pump), we have generated individual mutants and characterized their heavy metal susceptibilities. The deletion of CrpA in A. nidulans has led to the increased sensitivity of the fungus to stresses induced by Zn 2+ , Fe 2+ , or the combination of oxidative-stress-inducing menadione sodium bisulfite and Fe 3+ . Heterologous expression of A. fumigatus PcaA in the S. cerevisiae pca1 deletion mutant has resulted in enhanced tolerance of the yeast to stresses elicited by Cd 2+ or Zn 2+ but not by Fe 2+ /Fe 3+ or Cu 2+ . Mammalian host immune defense can attack microbes by secreting Zn 2+ or Cu 2+ , and the oxidative stress induced by host immune systems can also disturb metal (Cu 2+ , Fe 2+ , and Zn 2+ ) homeostasis in microbes. In summary, PcaA and CrpA can protect fungal cells from these complex stresses that contribute to the virulence of the pathogenic Aspergillus species. Moreover, due to their presence on the fungal cell surface, these P 1B -type ATPases may serve as a novel drug target in the future. IMPORTANCE Mammalian host immune defense disrupts heavy metal homeostasis of fungal pathogens. P1B-type ATPase of Aspergillus fumigatus and Aspergillus nidulans may help to cope with this stress and serve as virulence traits. In our experiments, both A. nidulans Cd2+/Cu2+ pump CrpA and A. fumigatus Cd2+ pump PcaA protected fungal cells from toxic Zn2+, and CrpA also decreased Fe2+ susceptibility most likely indirectly. In addition, CrpA protected cells against the combined stress induced by the oxidative stressor menadione and Fe3+. Since P1B-type ATPases are present on the fungal cell surface, these proteins may serve as a novel drug target in the future.

Funder

Nemzeti Kutatási Fejlesztési és Innovációs Hivatal

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3