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Leishmania LABCG1 and LABCG2 transporters are involved in virulence and oxidative stress: functional linkage with autophagy

Overview of attention for article published in Parasites & Vectors, May 2017
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Title
Leishmania LABCG1 and LABCG2 transporters are involved in virulence and oxidative stress: functional linkage with autophagy
Published in
Parasites & Vectors, May 2017
DOI 10.1186/s13071-017-2198-1
Pubmed ID
Authors

José Ignacio Manzano, Ana Perea, David León-Guerrero, Jenny Campos-Salinas, Lucia Piacenza, Santiago Castanys, Francisco Gamarro

Abstract

The G subfamily of ABC (ATP-binding cassette) transporters of Leishmania include 6 genes (ABCG1-G6), some with relevant biological functions associated with drug resistance and phospholipid transport. Several studies have shown that Leishmania LABCG2 transporter plays a role in the exposure of phosphatidylserine (PS), in virulence and in resistance to antimonials. However, the involvement of this transporter in other key biological processes has not been studied. To better understand the biological function of LABCG2 and its nearly identical tandem-repeated transporter LABCG1, we have generated Leishmania major null mutant parasites for both genes (ΔLABCG1-2). NBD-PS uptake, infectivity, metacyclogenesis, autophagy and thiols were measured. Leishmania major ΔLABCG1-2 parasites present a reduction in NBD-PS uptake, infectivity and virulence. In addition, we have shown that ΔLABCG1-2 parasites in stationary phase growth underwent less metacyclogenesis and presented differences in the plasma membrane's lipophosphoglycan composition. Considering that autophagy is an important process in terms of parasite virulence and cell differentiation, we have shown an autophagy defect in ΔLABCG1-2 parasites, detected by monitoring expression of the autophagosome marker RFP-ATG8. This defect correlates with increased levels of reactive oxygen species and higher non-protein thiol content in ΔLABCG1-2 parasites. HPLC analysis revealed that trypanothione and glutathione were the main molecules accumulated in these ΔLABCG1-2 parasites. The decrease in non-protein thiol levels due to preincubation with buthionine sulphoximide (a γ-glutamylcysteine synthetase inhibitor) restored the autophagy process in ΔLABCG1-2 parasites, indicating a relationship between autophagy and thiol content. LABCG1-2 transporters from Leishmania could be considered as phosphatidylserine and non-protein thiol transporters. They probably accomplish transportation in conjunction with other molecules that are involved in oxidative stress, autophagy, metacyclogenesis and infectivity processes. The overall conclusion is that LABCG1-2 transporters could play a key role in Leishmania cell survival and infectivity.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 22%
Student > Bachelor 4 22%
Student > Doctoral Student 3 17%
Researcher 2 11%
Student > Master 1 6%
Other 1 6%
Unknown 3 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 33%
Agricultural and Biological Sciences 4 22%
Immunology and Microbiology 2 11%
Medicine and Dentistry 1 6%
Unknown 5 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 June 2017.
All research outputs
#9,939,979
of 11,218,844 outputs
Outputs from Parasites & Vectors
#2,443
of 2,813 outputs
Outputs of similar age
#222,181
of 266,464 outputs
Outputs of similar age from Parasites & Vectors
#147
of 147 outputs
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So far Altmetric has tracked 2,813 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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