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

Area of Science:

• Immunology
• Microbiology
• Genetics

Background:

• Human Ribonuclease 6 (RNase 6) is a protein derived from monocytes and macrophages with antimicrobial properties.
• The RNASE6 gene exhibits genetic variation due to single nucleotide polymorphisms (SNPs), influencing protein function.
• rs1045922 is a common non-synonymous SNP in RNASE6, leading to an arginine (R) to glutamine (Q) substitution at position 66 (R66Q).

Purpose of the Study:

• To investigate the antimicrobial activity of RNase 6 R66 and Q66 variants against uropathogenic Escherichia coli (UPEC).
• To understand how the R66Q substitution affects the protein's electrostatic charge and bacterial interaction.
• To explore the potential impact of RNASE6 SNP distribution on susceptibility to urinary tract infections (UTIs).

Main Methods:

• Generation of recombinant RNase 6 R66 and Q66 protein variants.
• Determination of antimicrobial activity against UPEC.
• Structural analysis to assess electrostatic charge changes.
• Evaluation of bacterial agglutination and lipopolysaccharide binding capabilities.

Main Results:

• The R66 variant, encoded by the major allele of SNP rs1045922, demonstrated significantly higher bactericidal activity against UPEC compared to the Q66 variant.
• The enhanced activity of the R66 variant was associated with increased lipopolysaccharide binding and bacterial agglutination.
• Enzymatic efficiency remained comparable between the R66 and Q66 variants.

Conclusions:

• The R66 variant of RNase 6 exhibits superior antimicrobial efficacy against UPEC, potentially due to altered surface charge and enhanced bacterial interaction.
• The common SNP rs1045922 in the RNASE6 gene may influence an individual's susceptibility to UTIs.
• Further research into RNASE6 SNP prevalence and its role in UTI susceptibility is warranted.