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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F23%3A00568233" target="_blank" >RIV/60077344:_____/23:00568233 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/23:00568233 RIV/00216224:90242/23:00133763 RIV/00216208:11310/23:10458025

Výsledek na webu

<a href="https://doi.org/10.15698/mic2023.02.790" target="_blank" >https://doi.org/10.15698/mic2023.02.790</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.15698/mic2023.02.790" target="_blank" >10.15698/mic2023.02.790</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

The surface proteins of parasitic protozoa mediate functions essential to survival within a host, including nutrient accumulation, environmental 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 towards persistence within vertebrate hosts. Significantly, a superfamily of invariant 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 directly 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 evolution of resistance.

Název v anglickém jazyce

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

Popis výsledku anglicky

The surface proteins of parasitic protozoa mediate functions essential to survival within a host, including nutrient accumulation, environmental 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 towards persistence within vertebrate hosts. Significantly, a superfamily of invariant 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 directly 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 evolution of resistance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Microbial cell

ISSN

2311-2638

e-ISSN

2311-2638

Svazek periodika

10

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

AT - Rakouská republika

Počet stran výsledku

18

Strana od-do

18-35

Kód UT WoS článku

000928489100001

EID výsledku v databázi Scopus

2-s2.0-85159431878