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

Result code in 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>
Alternative codes found
RIV/61388963:_____/23:00568233 RIV/00216224:90242/23:00133763 RIV/00216208:11310/23:10458025
Result on the web
<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>

Result language
angličtina
Original language name
The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology

Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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