Iron economy in Naegleria gruberi reflects its metabolic flexibility

Mach, Jan; Bíla, Jarmila; Ženíšková, Kateřina; Arbon, Dominik; Malych, Ronald; Glavanakovová, Marie; Nývltová, Eva; Šuták, Robert

doi:10.1016/j.ijpara.2018.03.005

Cited by 20 publications

(26 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The overall changes in cellular processes in the iron-deficient conditions discussed in this paper are illustrated in Fig 2. These findings are in agreement with our previous study focused on iron metabolism in the nonpathogenic model organism N. gruberi [34], where the mitochondrion was shown to be the center of the iron economy. Together, these results show that iron deficiency is a highly unfavorable condition for N. fowleri , and targeted interference with its uptake could be an effective method of controlling the propagation or viability of this organism in the host.…”

Section: Discussionsupporting

confidence: 93%

“…Consistent with our previous study of iron metabolism in N. gruberi [34], hemerythrin was dramatically downregulated in iron-deficient conditions, while its expression appeared to be high, based on the intensities obtained in proteomic data from iron-rich cells. The involvement of hemerythrin in the iron metabolism of Naegleria is suggestive but unclear.…”

Section: Discussionsupporting

confidence: 91%

“…N. fowleri , as well as N. gruberi, possesses an AOX in the mitochondria, and our work indicates one of the possible advantages of this respiratory chain element for these organisms. Under iron-deficient conditions, the activity of AOX was significantly increased, even though it required iron, suggesting that this unusual branch of the respiratory chain takes over a portion of the activity in the iron-demanding conventional pathway of respiratory complexes III, IV and cytochrome c, an observation noted in the nonpathogenic amoeba N. gruberi previously [34]. This represents a favorable compensation pathway, even though the overall generation of the proton gradient and therefore ATP synthesis is hindered.…”

Section: Discussionmentioning

confidence: 72%

“…Label-free proteomic analysis of the samples was assessed using the method described in Mach et al 2018 [34], utilizing liquid chromatography coupled with mass spectrometry. The resulting MS/MS spectra were compared with the Naegleria fowleri database, downloaded from amoebaDB [42] on 25/7/2017.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Adaptive iron utilization compensates for the lack of an inducible uptake system inNaegleria fowleriand represents a potential target for therapeutic intervention

Arbon

Ženíšková

Mach

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Warm fresh water is a natural habitat for many single-celled organisms, including protozoan parasites such as the infamous brain-eating amoeba, Naegleria fowleri, which can become pathogenic for mammals, including humans. The condition caused by N. fowleri is known as primary amoebic meningoencephalitis, which is a generic and usually fatal infection of the brain with rapid onset. One of the important factors influencing a wide spectrum of pathogens, including N. fowleri, is the bioavailability of iron in the environment. The strategy of withholding iron evolved in mammalian hosts, and the different strategies of pathogens to obtain it are an important part of host-parasite interactions.In the present study, we employ different biochemical and analytical methods to explore the effect of decreased iron availability on the cellular processes of N. fowleri. We show that under iron starvation, nonessential, iron-dependent, mostly cytosolic pathways in N. fowleri are downregulated, while the metal is utilized in the mitochondria to maintain vital respiratory processes. Surprisingly, N. fowleri fails to respond to acute shortages of iron by the induction of a reductive iron uptake system that seems to be the main iron-obtaining strategy of the parasite. Our work aims to demonstrate the importance of mitochondrial iron in the biology of N. fowleri and to explore the plausibility of exploiting it as a potential target for therapeutic interference.Author SummaryNaegleria fowleri is undoubtedly one of the deadliest parasites of humans, hence the name “brain-eating amoeba”. Being dangerous, but rare, it may be regarded as a highly understudied pathogen of humans. Unfortunately, the symptoms of primary amoebic meningoencephalitis may be confused with much more common bacterial meningoencephalitis; therefore, it is quite probable that many infections caused by N. fowleri have been misdiagnosed as bacterial infections without further inquiry. In many cases, fast diagnosis is vital for commencing the correct therapy, and even then, complete success of the treatment is very rare. Our laboratory focuses on the uptake and intracellular metabolism of metals in unicellular eukaryotes, so we decided to explore the biology of N. fowleri from this aspect. Changes in the proteome, as a direct effect of iron-deficient conditions, were described, and these data were used to further explore the ways in which N. fowleri responds to these conditions on a cellular level and how its biology changes. Based on these findings, we propose that the struggle of N. fowleri to obtain iron from its host could be exploited for therapeutic interference purposes in primary amoebic meningoencephalitis patients.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 72%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Adaptive iron utilization compensates for the lack of an inducible uptake system inNaegleria fowleriand represents a potential target for therapeutic intervention

Arbon

Ženíšková

Mach

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…34 Peptides were analyzed on an Orbitrap Fusion system as described previously. 35 Proteins were identified with the Proteome Discoverer 1.4 software using a search against the ORCAE database. 36…”

Section: Purification and Identification Of The Iron-binding Protein mentioning

confidence: 99%

Copper and iron metabolism in Ostreococcus tauri – the role of phytotransferrin, plastocyanin and a chloroplast copper-transporting ATPase

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

Flow cytometry-based study of model marine microalgal consortia revealed an ecological advantage of siderophore utilization by the dinoflagellate Amphidinium carterae

Malych

Stopka

Mach

et al. 2022

Computational and Structural Biotechnology Journal

Self Cite

View full text Add to dashboard Cite

show abstract

Iron economy in Naegleria gruberi reflects its metabolic flexibility

Cited by 20 publications

References 46 publications

Adaptive iron utilization compensates for the lack of an inducible uptake system inNaegleria fowleriand represents a potential target for therapeutic intervention

Adaptive iron utilization compensates for the lack of an inducible uptake system inNaegleria fowleriand represents a potential target for therapeutic intervention

Copper and iron metabolism in Ostreococcus tauri – the role of phytotransferrin, plastocyanin and a chloroplast copper-transporting ATPase

Flow cytometry-based study of model marine microalgal consortia revealed an ecological advantage of siderophore utilization by the dinoflagellate Amphidinium carterae

Contact Info

Product

Resources

About