The role of invariant surface glycoprotein 75 in xenobiotic
acquisition by African trypanosomes

J 2023

The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes

MAKAROV, Alexandr, Jakub BEGAN, Ileana Corvo MAUTONE, Erika PINTO, Liam FERGUSON et. al.

Basic information

Original name

The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes

Authors

MAKAROV, Alexandr, Jakub BEGAN, Ileana Corvo MAUTONE, Erika PINTO, Liam FERGUSON, Martin ZOLTNER, Sebastian ZOLL and Mark C FIELD (guarantor)

Edition

MICROBIAL CELL, AUSTRIA, SHARED SCIENCE PUBLISHERS OG, 2023, 2311-2638

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

Austria

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.600 in 2022

RIV identification code

RIV/00216224:90242/23:00133763

DOI

http://dx.doi.org/10.15698/mic2023.02.790

UT WoS

000928489100001

Keywords in English

invariant surface glycoprotein; trypanosome; suramin; drug metabolism; drug accumulation; CRISPR; Cas9; xenobiotics

Abstract

V originále

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.

Links

90242, large research infrastructures

Name: CIISB III

Citovat

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. 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.

@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.

Detailed Information on Publication Record