Publication detail

G-quadruplexes in helminth parasites

CANTARA, A. LUO, Y. DOBROVOLNÁ, M. BOHALOVA, N. FOJTA, M. VERGA, D. GUITTAT, L. CUCCHIARINI, A. SAVRIMOUTOU, S. HÄBERLI, C. GUILLON, J. KEISER, J. MERGNY, J-L. BRÁZDA, V.

Original Title

Type

journal article in Web of Science

Language

English

Original Abstract

Parasitic helminths infecting humans are highly prevalent infecting similar to 2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the primary cause of morbidity. In addition, helminth infections of cattle have a significant economic impact on livestock production, milk yield and fertility. The etiological agents of helminth infections are mainly Nematodes (roundworms) and Platyhelminths (flatworms). G-quadruplexes (G4) are unusual nucleic acid structures formed by G-rich sequences that can be recognized by specific G4 ligands. Here we used the G4Hunter Web Tool to identify and compare potential G4 sequences (PQS) in the nuclear and mitochondrial genomes of various helminths to identify G4 ligand targets. PQS are nonrandomly distributed in these genomes and often located in the proximity of genes. Unexpectedly, a Nematode, Ascaris lumbricoides, was found to be highly enriched in stable PQS. This species can tolerate high-stability G4 structures, which are not counter selected at all, in stark contrast to most other species. We experimentally confirmed G4 formation for sequences found in four different parasitic helminths. Small molecules able to selectively recognize G4 were found to bind to Schistosoma mansoni G4 motifs. Two of these ligands demonstrated potent activity both against larval and adult stages of this parasite.

Keywords

G-quadruplexes; Parasites; Helminth; Schistosoma

Authors

CANTARA, A.; LUO, Y.; DOBROVOLNÁ, M.; BOHALOVA, N.; FOJTA, M.; VERGA, D.; GUITTAT, L.; CUCCHIARINI, A.; SAVRIMOUTOU, S.; HÄBERLI, C.; GUILLON, J.; KEISER, J.; MERGNY, J-L.; BRÁZDA, V.

Released

2. 3. 2022

Publisher

OXFORD UNIV PRESS

Location

OXFORD

ISBN

1362-4962

Periodical

Nucleic Acids Research

Year of study

Number

State

United Kingdom of Great Britain and Northern Ireland

Pages from

2719

Pages to

2735

Pages count

URL

https://academic.oup.com/nar/article/50/5/2719/6541030?login=false

BibTex

@article{BUT187732,
  author="CANTARA, A. and LUO, Y. and DOBROVOLNÁ, M. and BOHALOVA, N. and FOJTA, M. and VERGA, D. and GUITTAT, L. and CUCCHIARINI, A. and SAVRIMOUTOU, S. and HÄBERLI, C. and GUILLON, J. and KEISER, J. and MERGNY, J-L. and BRÁZDA, V.",
  title="G-quadruplexes in helminth parasites",
  journal="Nucleic Acids Research",
  year="2022",
  volume="50",
  number="5",
  pages="2719--2735",
  doi="10.1093/nar/gkac129",
  issn="1362-4962",
  url="https://academic.oup.com/nar/article/50/5/2719/6541030?login=false"
}