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@article{2383578,
author = {Makarov, Alexandr and Began, Jakub and Mautone, Ileana Corvo and Pinto, Erika and Ferguson, Liam and Zoltner, Martin and Zoll, Sebastian and Field, Mark C},
article_location = {AUSTRIA},
article_number = {2},
doi = {http://dx.doi.org/10.15698/mic2023.02.790},
keywords = {invariant surface glycoprotein; trypanosome; suramin; drug metabolism; drug accumulation; CRISPR; Cas9; xenobiotics},
language = {eng},
issn = {2311-2638},
journal = {MICROBIAL CELL},
title = {The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes},
url = {https://microbialcell.com/researcharticles/2023a-makarov-microbial-cell/},
volume = {10},
year = {2023}
}
TY - JOUR
ID - 2383578
AU - Makarov, Alexandr - Began, Jakub - Mautone, Ileana Corvo - Pinto, Erika - Ferguson, Liam - Zoltner, Martin - Zoll, Sebastian - Field, Mark C
PY - 2023
TI - The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes
JF - MICROBIAL CELL
VL - 10
IS - 2
SP - 18-35
EP - 18-35
PB - SHARED SCIENCE PUBLISHERS OG
SN - 23112638
KW - invariant surface glycoprotein
KW - trypanosome
KW - suramin
KW - drug metabolism
KW - drug accumulation
KW - CRISPR
KW - Cas9
KW - xenobiotics
UR - https://microbialcell.com/researcharticles/2023a-makarov-microbial-cell/
N2 - The surface proteins of parasitic protozoa mediate functions es-sential to survival within a host, including nutrient accumulation, environ-mental sensing and immune evasion. Several receptors involved in nutrient uptake and defence from the innate immune response have been described in African trypanosomes and, together with antigenic variation, contribute to-wards persistence within vertebrate hosts. Significantly, a superfamily of in-variant surface glycoproteins (ISGs) populates the trypanosome surface, one of which, ISG75, is implicated in uptake of the century-old drug suramin. By CRISPR/Cas9 knockout and biophysical analysis, we show here that ISG75 di-rectly binds suramin and mediates uptake of additional naphthol-related compounds, making ISG75 a conduit for entry of at least one structural class of trypanocidal compounds. However, ISG75 null cells present only modest attenuation of suramin sensitivity, have unaltered viability in vivo and in vitro and no alteration to suramin-invoked proteome responses. While ISG75 is demonstrated as a valid suramin cell entry pathway, we suggest the presence of additional mechanisms for suramin accumulation, further demonstrating the complexity of trypanosomatid drug interactions and potential for evolu-tion of resistance.
ER -
MAKAROV, Alexandr, Jakub BEGAN, Ileana Corvo MAUTONE, Erika PINTO, Liam FERGUSON, Martin ZOLTNER, Sebastian ZOLL and Mark C FIELD. The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes. \textit{MICROBIAL CELL}. AUSTRIA: SHARED SCIENCE PUBLISHERS OG, 2023, vol.~10, No~2, p.~18-35. ISSN~2311-2638. Available from: https://dx.doi.org/10.15698/mic2023.02.790.
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