Abstract:
BACKGROUND:Leishmania uses the amino acid L-arginine as a substrate for arginase, enzyme that produces urea and ornithine, last precursor of polyamine pathway. This pathway is used by the parasite to replicate and it is essential to establish the infection in the mammalian host. L-arginine is not synthesized by the parasite, so its uptake occurs through the amino acid permease 3 (AAP3). AAP3 is codified by two copies genes (5.1 and 4.7 copies), organized in tandem in the parasite genome. One copy presents the expression regulated by L-arginine availability. METHODOLOGY/PRINCIPAL FINDINGS:RNA-seq data revealed 14 amino acid transporters differentially expressed in the comparison of La-WT vs. La-arg- promastigotes and axenic amastigotes. The 5.1 and 4.7 aap3 transcripts were down-regulated in La-WT promastigotes vs. axenic amastigotes, and in La-WT vs. La-arg- promastigotes. In contrast, transcripts of other transporters were up-regulated in the same comparisons. The amount of 5.1 and 4.7 aap3 mRNA of intracellular amastigotes was also determined in sample preparations from macrophages, obtained from BALB/c and C57BL/6 mice and the human THP-1 lineage infected with La-WT or La-arg-, revealing that the genetic host background is also important. We also determined the aap3 mRNA and AAP3 protein amounts of promastigotes and axenic amastigotes in different environmental growth conditions, varying pH, temperature and L-arginine availability. Interestingly, the increase of temperature increased the AAP3 level in plasma membrane and consequently the L-arginine uptake, independently of pH and L-arginine availability. In addition, we demonstrated that besides the plasma membrane localization, AAP3 was also localized in the glycosome of L. amazonensis promastigotes and axenic amastigotes. CONCLUSIONS/SIGNIFICANCE:In this report, we described the differential transcriptional profiling of amino acids transporters from La-WT and La-arg- promastigotes and axenic amastigotes. We also showed the increased AAP3 levels under amino acid starvation or its decrease in L-arginine supplementation. The differential AAP3 expression was determined in the differentiation of promastigotes to amastigotes conditions, as well as the detection of AAP3 in the plasma membrane reflecting in the L-arginine uptake. Our data suggest that depending on the amino acid pool and arginase activity, Leishmania senses and could use an alternative route for the amino acid transport in response to stress signaling.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Aoki JI,Muxel SM,Zampieri RA,Acuña SM,Fernandes JCR,Vanderlinde RH,Sales MCOP,Floeter-Winter LMdoi
10.1371/journal.pntd.0006025subject
Has Abstractpub_date
2017-10-26 00:00:00pages
e0006025issue
10eissn
1935-2727issn
1935-2735pii
PNTD-D-17-00796journal_volume
11pub_type
杂志文章abstract:BACKGROUND:The rapid spread of Zika virus in the Americas and current outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses. METHODOLOGY/PRINCIPAL FINDINGS:We report a case of a 20-year-old pregnant woman who was referred to our service after a l...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004517
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abstract:BACKGROUND:The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO) levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi control. Howe...
journal_title:PLoS neglected tropical diseases
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doi:10.1371/journal.pntd.0001644
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journal_title:PLoS neglected tropical diseases
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doi:10.1371/journal.pntd.0003252
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abstract::Erythema nodosum leprosum (ENL), or type 2 lepra reaction, is a multi-system immune-mediated complication in patients with multibacillary leprosy, frequently associated with chronicity and recurrences. Management of ENL requires high doses of oral corticosteroids, which may not be universally effective and pose seriou...
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abstract:BACKGROUND:Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for rea...
journal_title:PLoS neglected tropical diseases
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doi:10.1371/journal.pntd.0001327
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abstract:BACKGROUND:Dengue is the most important mosquito-borne viral disease affecting humans. The only prevention measure currently available is the control of its vectors, primarily Aedes aegypti. Recent advances in genetic engineering have opened the possibility for a new range of control strategies based on genetically mod...
journal_title:PLoS neglected tropical diseases
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doi:10.1371/journal.pntd.0000508
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abstract::Salmonella Typhimurium sequence type (ST) 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve...
journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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doi:10.1371/journal.pntd.0000672
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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pub_type: 杂志文章
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
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更新日期:2015-01-08 00:00:00
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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doi:10.1371/journal.pntd.0001200
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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更新日期:2020-05-13 00:00:00
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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更新日期:2011-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1371/journal.pntd.0002574
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