A Common Polymorphism in RNASE6 Impacts Its Antimicrobial Activity toward Uropathogenic Escherichia coli
Anguita, Raúl (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Prats-Ejarque, Guillem (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Moussaoui, Mohammed (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Becknell, Brian (The Abigail Wexner Research Institute at Nationwide Children's Hospital)
Boix i Borràs, Esther (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2024
Abstract:	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.
Grants:	Agencia Estatal de Investigación PID2019-106123GB-I00 Agencia Estatal de Investigación PID2022-137872NB-100
Rights:	Aquest 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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	RNase ; Single nucleotide polymorphisms ; Antimicrobial peptides ; Urinary tract infections ; Uropathogenic Escherichia coli
Published in:	International journal of molecular sciences, Vol. 25, Issue 1 (January 2024) , art. 604, ISSN 1422-0067

DOI: 10.3390/ijms25010604
PMID: 38203775

10 p, 1.5 MB

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