scholarly journals The major surface protease (MSP or GP63) in the intracellular amastigote stage of Leishmania chagasi

2008 ◽  
Vol 157 (2) ◽  
pp. 148-159 ◽  
Author(s):  
Chia-Hung Christine Hsiao ◽  
Chaoqun Yao ◽  
Patricia Storlie ◽  
John E. Donelson ◽  
Mary E. Wilson
Keyword(s):  
Leishmania Chagasi ◽  
Amastigote Stage ◽  
Major Surface ◽  
Intracellular Amastigote

Genomic diversity in the Leishmania donovani complex

Parasitology ◽  
1999 ◽  
Vol 119 (3) ◽  
pp. 237-246 ◽  
Author(s):  
I. L. MAURICIO ◽  
M. K. HOWARD ◽  
J. R. STOTHARD ◽  
M. A. MILES
Keyword(s):  
New World ◽  
Leishmania Donovani ◽  
Single Gene ◽  
Genomic Diversity ◽  
Leishmania Chagasi ◽  
Old World ◽  
Partial Sequencing ◽  
Random Amplification ◽  
Major Surface ◽  
Different Levels

The Leishmania donovani complex is considered to be composed of 3 species; L. donovani, L. infantum and L. chagasi, although this classification has been challenged. Genotypic relationships within the complex were evaluated at different levels by: binding of the probe Lmet9, specific for L. chagasi and Old World Leishmania spp.; partial sequencing of a constitutive major surface protease single gene (mspC) and random amplification of polymorphic DNA (RAPD). The Old World Leishmania spp. and the L. donovani complex have a monophyletic origin. Leishmania chagasi clearly belongs to the L. donovani complex but it is indistinguishable from L. infantum, which suggests introduction of L. chagasi into the New World in recent history. Leishmania infantum/L. chagasi was identified as a monophyletic group within the L. donovani complex but L. donovani may be paraphyletic. Diversity within L. donovani is substantial and phylogeographical patterns of association were found.

scholarly journals Genomic and Metabolomic Polymorphism among Experimentally Selected Paromomycin-Resistant Leishmania donovani Strains

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
C. D. Shaw ◽  
H. Imamura ◽  
T. Downing ◽  
G. Blackburn ◽  
G. D. Westrop ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Wild Type ◽  
Genetic Changes ◽  
Content Type ◽  
Novel Treatments ◽  
Branched Chain Amino Acid ◽  
Amastigote Stage ◽  
Branched Chain ◽  
Intracellular Amastigote ◽  
Selection Of

ABSTRACT Understanding the mechanism(s) underpinning drug resistance could lead to novel treatments to reverse the increased tolerance of a pathogen. In this study, paromomycin (PMM) resistance (PMMr) was induced in three Nepalese clinical strains of Leishmania donovani with different inherent susceptibilities to antimony (Sb) drugs by stepwise exposure of promastigotes to PMM. Exposure to PMM resulted in the production of mixed populations of parasites, even though a single cloned population was used at the start of selection. PMM 50% inhibitory concentration (IC50) values for PMMr parasites varied between 104 and 481 μM at the promastigote stage and 32 and 195 μM at the intracellular amastigote stage. PMM resistance was associated with increased resistance to nitric oxide at the amastigote stage but not the promastigote stage (P < 0.05). This effect was most marked in the Sb-resistant (Sbr) PMMr clone, in which PMM resistance was associated with a significant upregulation of glutathione compared to that in its wild type (P < 0.05), although there was no change in the regulation of trypanothione (detected in its oxidized form). Interestingly, PMMr strains showed an increase in either the keto acid derivative of isoleucine (Sb intermediate PMMr) or the 2-hydroxy acids derived from arginine and tyrosine (Sb susceptible PMMr and Sbr PMMr). These results are consistent with the recent finding that the upregulation of the branched-chain amino acid aminotransferase and d-lactate dehydrogenase is linked to PMMr. In addition, we found that PMMr is associated with a significant increase in aneuploidy during PMM selection in all the strains, which could allow the rapid selection of genetic changes that confer a survival advantage.

Biosynthesis of the major surface protease GP63 of Leishmania chagasi

2002 ◽  
Vol 121 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Chaoqun Yao ◽  
Kevin G. Leidal ◽  
Andrew Brittingham ◽  
Deirdre E. Tarr ◽  
John E. Donelson ◽  
...  
Keyword(s):  
Leishmania Chagasi ◽  
Major Surface

Multiple products of the Leishmania chagasi major surface protease (MSP or GP63) gene family

2004 ◽  
Vol 135 (2) ◽  
pp. 171-183 ◽  
Author(s):  
Chaoqun Yao ◽  
Jiwen Luo ◽  
Patricia Storlie ◽  
John E. Donelson ◽  
Mary E. Wilson
Keyword(s):  
Gene Family ◽  
Leishmania Chagasi ◽  
Multiple Products ◽  
Major Surface

Characterization of major surface protease (MSP) in axenic cultured amastigotes of Leishmania chagasi

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Chia‐Hung Christine Hsiao ◽  
Chaoqun Yao ◽  
John E Donelson ◽  
Mary E Wilson
Keyword(s):  
Leishmania Chagasi ◽  
Major Surface

scholarly journals Internal and Surface-Localized Major Surface Proteases of Leishmania spp. and Their Differential Release from Promastigotes

2007 ◽  
Vol 6 (10) ◽  
pp. 1905-1912 ◽  
Author(s):  
Chaoqun Yao ◽  
John E. Donelson ◽  
Mary E. Wilson
Keyword(s):  
Surface Membrane ◽  
Sand Fly ◽  
Dependent Manner ◽  
Leishmania Chagasi ◽  
Metacyclic Promastigotes ◽  
Basement Membrane Extract ◽  
Leishmania Spp ◽  
Major Surface ◽  
Dose Dependent ◽  
Extracellular Environment

ABSTRACT Major surface protease (MSP), also called GP63, is a virulence factor of Leishmania spp. protozoa. There are three pools of MSP, located either internally within the parasite, anchored to the surface membrane, or released into the extracellular environment. The regulation and biological functions of these MSP pools are unknown. We investigated here the trafficking and extrusion of surface versus internal MSPs. Virulent Leishmania chagasi undergo a growth-associated lengthening in the t 1/2 of surface-localized MSP, but this did not occur in the attenuated L5 strain. The release of surface-localized MSP was enhanced in a dose-dependent manner by MβCD, which chelates membrane cholesterol-ergosterol. Furthermore, incubation of promastigotes at 37°C with Matrigel matrix, a soluble basement membrane extract of Engelbreth-Holm-Swarm tumor cells, stimulated the release of internal MSP but not of surface-located MSP. Taken together, these data indicate that MSP subpopulations in distinct cellular locations are released from the parasite under different environmental conditions. We hypothesize that the internal MSP with its lengthy t 1/2 does not serve as a pool for promastigote surface MSP in the sand fly vector but that it instead functions as an MSP pool ready for quick release upon inoculation of metacyclic promastigotes into mammals. We present a model in which these different MSP pools are released under distinct life cycle-specific conditions.

Internal and surface subpopulations of the major surface protease (MSP) of Leishmania chagasi

2005 ◽  
Vol 139 (2) ◽  
pp. 173-183 ◽  
Author(s):  
Chaoqun Yao ◽  
Jiwen Luo ◽  
Christine Hsiao ◽  
John E. Donelson ◽  
Mary E. Wilson
Keyword(s):  
Leishmania Chagasi ◽  
Major Surface

The gene B protein localises to the surface of Leishmania major parasites in the absence of metacyclic stage lipophosphoglycan

1995 ◽  
Vol 108 (11) ◽  
pp. 3359-3366 ◽  
Author(s):  
D. Rangarajan ◽  
S. Gokool ◽  
M.V. McCrossan ◽  
D.F. Smith
Keyword(s):  
Cell Surface ◽  
Leishmania Major ◽  
Specific Gene ◽  
Developmentally Regulated ◽  
Amastigote Stage ◽  
Intracellular Amastigote

The stage specific Gene B protein (GBP) of Leishmania major localises to the surface of infective metacyclic parasites, where it associates with the developmentally regulated surface glycoconjugate, lipophosphoglycan (LPG). This association has been proposed to aid maintenance of GBP on the parasite surface. In this paper, we show that the abundance of GBP on the extracellular metacyclic cell surface is in the order of 100,000 copies per cell. This level of expression is comparable to that seen in the intracellular amastigote stage, in which GBP is also localised to the surface, despite the lack of metacyclic stage specific LPG. Furthermore GBP expressed from an episome in avirulent parasites, which are unable to synthesise metacyclic LPG or endogenous GBP, also localises to the parasite surface. These data demonstrate that GBP can maintain a surface localisation in the absence of metacyclic LPG, suggesting that it is able to associate with other glycoconjugates on the surface of infective parasites.

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