A Common Polymorphism in <i>RNASE6</i> Impacts Its Antimicrobial Activity toward Uropathogenic <i>Escherichia coli</i>
Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent antimicrobial activity toward uropathogenic bacteria. The <i>RNASE6</i> gene is heterogeneous in humans due to the presence of single nucleotide polymorphisms (SNPs). <i>RNASE6</i> rs1045922...
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/604 |
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| author | Raul Anguita Guillem Prats-Ejarque Mohammed Moussaoui Brian Becknell Ester Boix |
| author_facet | Raul Anguita Guillem Prats-Ejarque Mohammed Moussaoui Brian Becknell Ester Boix |
| author_sort | Raul Anguita |
| collection | DOAJ |
| description | Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent antimicrobial activity toward uropathogenic bacteria. The <i>RNASE6</i> gene is heterogeneous in humans due to the presence of single nucleotide polymorphisms (SNPs). <i>RNASE6</i> 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 <i>Escherichia coli</i> (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 <i>RNASE6</i> SNP distribution and its impact in UTI susceptibility. |
| first_indexed | 2024-03-08T15:04:34Z |
| format | Article |
| id | doaj.art-47a1213ccd9a4cc591e84e070fe3c700 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:04:34Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-47a1213ccd9a4cc591e84e070fe3c7002024-01-10T15:00:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125160410.3390/ijms25010604A Common Polymorphism in <i>RNASE6</i> Impacts Its Antimicrobial Activity toward Uropathogenic <i>Escherichia coli</i>Raul Anguita0Guillem Prats-Ejarque1Mohammed Moussaoui2Brian Becknell3Ester Boix4Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainKidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USADepartment of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, SpainHuman Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent antimicrobial activity toward uropathogenic bacteria. The <i>RNASE6</i> gene is heterogeneous in humans due to the presence of single nucleotide polymorphisms (SNPs). <i>RNASE6</i> 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 <i>Escherichia coli</i> (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 <i>RNASE6</i> SNP distribution and its impact in UTI susceptibility.https://www.mdpi.com/1422-0067/25/1/604RNaseRNase 6RNase k6single nucleotide polymorphismsantimicrobial peptidesurinary tract infections |
| spellingShingle | Raul Anguita Guillem Prats-Ejarque Mohammed Moussaoui Brian Becknell Ester Boix A Common Polymorphism in <i>RNASE6</i> Impacts Its Antimicrobial Activity toward Uropathogenic <i>Escherichia coli</i> International Journal of Molecular Sciences RNase RNase 6 RNase k6 single nucleotide polymorphisms antimicrobial peptides urinary tract infections |
| title | A Common Polymorphism in <i>RNASE6</i> Impacts Its Antimicrobial Activity toward Uropathogenic <i>Escherichia coli</i> |
| title_full | A Common Polymorphism in <i>RNASE6</i> Impacts Its Antimicrobial Activity toward Uropathogenic <i>Escherichia coli</i> |
| title_fullStr | A Common Polymorphism in <i>RNASE6</i> Impacts Its Antimicrobial Activity toward Uropathogenic <i>Escherichia coli</i> |
| title_full_unstemmed | A Common Polymorphism in <i>RNASE6</i> Impacts Its Antimicrobial Activity toward Uropathogenic <i>Escherichia coli</i> |
| title_short | A Common Polymorphism in <i>RNASE6</i> Impacts Its Antimicrobial Activity toward Uropathogenic <i>Escherichia coli</i> |
| title_sort | common polymorphism in i rnase6 i impacts its antimicrobial activity toward uropathogenic i escherichia coli i |
| topic | RNase RNase 6 RNase k6 single nucleotide polymorphisms antimicrobial peptides urinary tract infections |
| url | https://www.mdpi.com/1422-0067/25/1/604 |
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