Zinc at the Host–Fungus Interface: How to Uptake the Metal?

Soares, Lucas Weba; Bailão, Alexandre Melo; Soares, Célia Maria de Almeida; Bailão, Mirelle Garcia Silva

doi:10.3390/jof6040305

Cited by 17 publications

(23 citation statements)

References 98 publications

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“…On the other hand, Zrt2 does not have to contend with high-affinity zincophores, but, for instance, it rather may be helped in zinc recruitment by the Sap6 protein. It is a secreted aspartyl protease involved in zinc acquisition, which can increase the metal local concentration and act as a zinc “magnet”, facilitating metal internalization by membrane transporters [ 6 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…acquisition, which can increase the metal local concentration and act as a zinc "magnet", facilitating metal internalization by membrane transporters [6,35].…”

Section: A Qualitative Evaluation Of Zrt2 Metal-binding Abilitymentioning

confidence: 99%

“…Two of them, Zrt1 and Zrt2, belonging to the ZIP family, were predicted to be localized in the plasma membrane. In particular, Zrt2 proved to be the major zinc importer in C. albicans, being crucial to acquire zinc under acidic conditions and cooperating with Zrt1 in the metal uptake at neutral/alkaline pH [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Zn2+ and Cu2+ Binding to the Extramembrane Loop of Zrt2, a Zinc Transporter of Candida albicans

et al. 2022

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Zrt2 is a zinc transporter of the ZIP family. It is predicted to be located in the plasma membrane and it is essential for Candida albicans zinc uptake and growth at acidic pH. Zrt2 from C. albicans is composed of 370 amino acids and contains eight putative transmembrane domains and an extra-membrane disordered loop, corresponding to the amino acid sequence 126–215. This protein region contains at least three possible metal binding motifs: HxHxHxxD (144–153), HxxHxxEHxD (181–193) and the Glu- and Asp- rich sequence DDEEEDxE (161–168). The corresponding model peptides, protected at their termini (Ac-GPHTHSHFGD-NH2, Ac-DDEEEDLE-NH2 and Ac-PSHFAHAQEHQDP-NH2), have been investigated in order to elucidate the thermodynamic and coordination properties of their Zn2+ and Cu2+ complexes, with the further aim to identify the most effective metal binding site among the three fragments. Furthermore, we extended the investigation to the peptides Ac-GPHTHAHFGD-NH2 and Ac-PAHFAHAQEHQDP-NH2, where serine residues have been substituted by alanines in order to check if the presence of a serine residue may favor the displacement of amidic protons by Cu2+. In the native Zrt2 protein, the Ac-GPHTHSHFGD-NH2 region of the Zrt2 loop has the highest metal binding affinity, showing that three alternated histidines separated by only one residue (-HxHxH-) bind Zn2+ and Cu2+ more strongly than the region in which three histidines are separated by two and three His residues (-HxxHxxxH- in Ac-PSHFAHAQEHQDP-NH2). All studied Zrt2 loop fragments have lower affinity towards Zn2+ than the zinc(II) binding site on the Zrt1 transporter; also, all three Zrt2 regions bind Zn2+ and Cu2+ with comparable affinity below pH 5 and, therefore, may equally contribute to the metal acquisition under the most acidic conditions in which the Zrt2 transporter is expressed.

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Section: Resultsmentioning

confidence: 99%

“…acquisition, which can increase the metal local concentration and act as a zinc "magnet", facilitating metal internalization by membrane transporters [6,35].…”

Section: A Qualitative Evaluation Of Zrt2 Metal-binding Abilitymentioning

confidence: 99%

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Zn2+ and Cu2+ Binding to the Extramembrane Loop of Zrt2, a Zinc Transporter of Candida albicans

et al. 2022

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“…The regulation of Yek4 is unknown whereas Msc2, and Cot1 regulation is not dependent on Zap1. Adapted from ( Soares et al., 2020 ).…”

Section: Regulation Of Zn 2+ Homeostasismentioning

confidence: 99%

“…The Zap1 transcription factor (coloured circle) is activated in a Zn 2+ -depleted environment and then targets and induces the expression of genes involved in Zn 2+ transport into and out of the cytoplasm. Adapted from ( Frey et al., 2011 ; Soares et al., 2020 ; Wilson et al., 2012 ).…”

Section: Zn 2+ Uptake and Compartmentalisationmentioning

confidence: 99%

Nutritional immunity: targeting fungal zinc homeostasis

Alamir

Oladele

Ibe

2021

Heliyon

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Transition metals, such as Zn 2þ , are essential dietary constituents of all biological life, including mammalian hosts and the pathogens that infect them. Therefore, to thrive and cause infection, pathogens must successfully assimilate these elements from the host milieu. Consequently, mammalian immunity has evolved to actively restrict and/or pool metals to toxic concentrations in an effort to attenuate microbial pathogenicity -a process termed nutritional immunity. Despite host-induced Zn 2þ nutritional immunity, pathogens such as Candida albicans, are still capable of causing disease and thus must be equipped with robust Zn 2þ sensory, uptake and detoxification machinery. This review will discuss the strategies employed by mammalian hosts to limit Zn 2þ during infection, and the subsequent fungal interventions that counteract Zn 2þ nutritional immunity.

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