A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli

Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent antimicrobial activity toward uropathogenic bacteria. The RNASE6 gene is heterogeneous in humans due to the presence of single nucleotide polymorphisms (SNPs). RNASE6 rs1045922 is the most common non-synonymous SNP...

ver descrição completa

Detalhes bibliográficos
Autores: Anguita, Raúl|||0000-0003-2491-4811, Prats-Ejarque, Guillem|||0000-0002-8213-4947, Moussaoui, Mohammed|||0000-0001-6694-7692, Becknell, Brian, Boix, Ester|||0000-0003-1790-2142
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:289019
Acesso em linha:https://ddd.uab.cat/record/289019
https://dx.doi.org/urn:doi:10.3390/ijms25010604
Access Level:acceso abierto
Palavra-chave:RNase
Single nucleotide polymorphisms
Antimicrobial peptides
Urinary tract infections
Uropathogenic Escherichia coli
id ES_7d2c56c9a7eb59daa49f4f170656cd96
oai_identifier_str oai:ddd.uab.cat:289019
network_acronym_str ES
network_name_str España
repository_id_str
spelling A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coliAnguita, Raúl|||0000-0003-2491-4811Prats-Ejarque, Guillem|||0000-0002-8213-4947Moussaoui, Mohammed|||0000-0001-6694-7692Becknell, BrianBoix, Ester|||0000-0003-1790-2142RNaseSingle nucleotide polymorphismsAntimicrobial peptidesUrinary tract infectionsUropathogenic Escherichia coliHuman Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent antimicrobial activity toward uropathogenic bacteria. The RNASE6 gene is heterogeneous in humans due to the presence of single nucleotide polymorphisms (SNPs). RNASE6 rs1045922 is the most common non-synonymous SNP, resulting in a G to A substitution that determines an arginine (R) to glutamine (Q) transversion at position 66 in the protein sequence. By structural analysis we observed that R66Q substitution significantly reduces the positive electrostatic charge at the protein surface. Here, we generated both recombinant RNase 6-R66 and -Q66 protein variants and determined their antimicrobial activity toward uropathogenic Escherichia coli (UPEC), the most common cause of UTI. We found that the R66 variant, encoded by the major SNP rs1045922 allele, exhibited superior bactericidal activity in comparison to the Q66 variant. The higher bactericidal activity of R66 variant correlated with an increase in the protein lipopolysaccharide binding and bacterial agglutination abilities, while retaining the same enzymatic efficiency. These findings encourage further work to evaluate RNASE6 SNP distribution and its impact in UTI susceptibility. 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/289019https://dx.doi.org/urn:doi:10.3390/ijms25010604reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-106123GB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-137872NB-100open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2890192026-06-06T12:50:31Z
dc.title.none.fl_str_mv A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
title A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
spellingShingle A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
Anguita, Raúl|||0000-0003-2491-4811
RNase
Single nucleotide polymorphisms
Antimicrobial peptides
Urinary tract infections
Uropathogenic Escherichia coli
title_short A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
title_full A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
title_fullStr A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
title_full_unstemmed A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
title_sort A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
dc.creator.none.fl_str_mv Anguita, Raúl|||0000-0003-2491-4811
Prats-Ejarque, Guillem|||0000-0002-8213-4947
Moussaoui, Mohammed|||0000-0001-6694-7692
Becknell, Brian
Boix, Ester|||0000-0003-1790-2142
author Anguita, Raúl|||0000-0003-2491-4811
author_facet Anguita, Raúl|||0000-0003-2491-4811
Prats-Ejarque, Guillem|||0000-0002-8213-4947
Moussaoui, Mohammed|||0000-0001-6694-7692
Becknell, Brian
Boix, Ester|||0000-0003-1790-2142
author_role author
author2 Prats-Ejarque, Guillem|||0000-0002-8213-4947
Moussaoui, Mohammed|||0000-0001-6694-7692
Becknell, Brian
Boix, Ester|||0000-0003-1790-2142
author2_role author
author
author
author
dc.subject.none.fl_str_mv RNase
Single nucleotide polymorphisms
Antimicrobial peptides
Urinary tract infections
Uropathogenic Escherichia coli
topic RNase
Single nucleotide polymorphisms
Antimicrobial peptides
Urinary tract infections
Uropathogenic Escherichia coli
description Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent antimicrobial activity toward uropathogenic bacteria. The RNASE6 gene is heterogeneous in humans due to the presence of single nucleotide polymorphisms (SNPs). RNASE6 rs1045922 is the most common non-synonymous SNP, resulting in a G to A substitution that determines an arginine (R) to glutamine (Q) transversion at position 66 in the protein sequence. By structural analysis we observed that R66Q substitution significantly reduces the positive electrostatic charge at the protein surface. Here, we generated both recombinant RNase 6-R66 and -Q66 protein variants and determined their antimicrobial activity toward uropathogenic Escherichia coli (UPEC), the most common cause of UTI. We found that the R66 variant, encoded by the major SNP rs1045922 allele, exhibited superior bactericidal activity in comparison to the Q66 variant. The higher bactericidal activity of R66 variant correlated with an increase in the protein lipopolysaccharide binding and bacterial agglutination abilities, while retaining the same enzymatic efficiency. These findings encourage further work to evaluate RNASE6 SNP distribution and its impact in UTI susceptibility.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/289019
https://dx.doi.org/urn:doi:10.3390/ijms25010604
url https://ddd.uab.cat/record/289019
https://dx.doi.org/urn:doi:10.3390/ijms25010604
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-106123GB-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-137872NB-100
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411644286697472
score 15.300724

Registos relacionados