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Aftpo3 and Afdur3, the Aspergillus fumigatus Plasma Membrane Transporters of Polyamines, Regulate Polyamine Homeostasis and Itraconazole Susceptibility

ABSTRACT:

Aspergillus fumigatus is a notorious opportunistic pathogen that causes Invasive Aspergillosis (IA) infections with high mortality in immunosuppressed individuals. Long-term antifungal drug azole abuse in clinical treatment and agriculture renders it ineffectual or drug resistant. Drug resistance can relate to the cellular metabolites and corresponding gene transcription. In this study, through untargeted metabolomics and transcriptomics following itraconazole (ITC) treatment we identified two plasma membrane-localized polyamine transporters Aftpo3 and Afdur3, which were important for polyamine homeostasis and ITC susceptibility in A. fumigatus. In the absence of Aftpo3 or Afdur3, the levels of cytoplasm polyamines had a moderate increase, accompanied by resistance to ITC. In comparison, overexpression of Aftpo3 or Afdur3 induced drastic increase of polyamines, which were linked with the sensitivity to ITC. Accordingly, our study demonstrated that concentration-dependence of polyamines affected susceptibility of A. fumigatus to ITC, by scavenging reactive oxygen species (ROS) at a moderate concentration or generating ROS at a high concentration rather than drug transport.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse phase

SUBMITTER: mingcong chen

PROVIDER: MTBLS1739 | MetaboLights | 2020-12-21

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS1739	Other
	FILES	Other
	a_MTBLS1739_LC-MS_alternating_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS1739_LC-MS_alternating_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Polyamines induce the glutamate decarboxylase acid response system by increasing the level of the σ38 subunit (RpoS) of Escherichia coli RNA polymerase via gadE regulon

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