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Association of variants in selected genes mediating host immune response with duration of Staphylococcus aureus bacteremia.

ABSTRACT: Host genetic variation may be a contributing factor to variability in Staphylococcus aureus bacteremia duration. We assessed whether 28 single nucleotide polymorphisms (SNPs) in seven genes (TLR2, TLR4, TIRAP, IRAK4, TRAF6, NOD2, and CISH) that mediate host immune response were associated with S. aureus bacteremia duration. Subjects included 158 patients with short-term (≤4 days) and 44 with persistent (>4 days) S. aureus bacteremia from an academic medical center. In single SNP analyses, the minor allele frequencies of three TIRAP SNPs (rs655540, rs563011, and rs8177376) were higher in persistent bacteremia (P < 0.05). A haplotype with all three minor alleles was also associated with persistent bacteremia (P = 0.037). The minor allele frequencies of four other TIRAP SNPs (rs8177342, rs4937114, rs3802813, and rs4937115) were higher in short-term bacteremia (P < 0.05), and a haplotype containing the four minor alleles was associated with short-term bacteremia (P = 0.045). All seven SNPs are located in binding sites for proteins or noncoding RNAs that regulate transcription. None of the associations remained statistically significant after adjustment for multiple comparisons. Further investigation is needed to understand how genetic variation in TIRAP and other host immune genes may influence the duration of S. aureus bacteremia.

SUBMITTER: Carter TC

PROVIDER: S-EPMC7449870 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Attempts to develop an efficient anti-staphylococcal vaccine in humans have so far been unsuccessful. Therefore, more knowledge of the antigens that are expressed by Staphylococcus aureus in human blood and induce an immune response in patients is required. In this study we further characterize the serial levels of IgG and IgA antibodies against 56 staphylococcal antigens in multiple serum samples of 21 patients with a S. aureus bacteremia, compare peak IgG levels between patients and 30 non-infected controls, and analyze the expression of 3626 genes by two genetically distinct isolates in human blood. The serum antibody levels were measured using a bead-based flow cytometry technique (xMAP®, Luminex corporation). Gene expression levels were analyzed using a microarray (BµG@s microarray). The initial levels and time taken to reach peak IgG and IgA antibody levels were heterogeneous in bacteremia patients. The antigen SA0688 was associated with the highest median initial-to-peak antibody fold-increase for IgG (5.05-fold) and the second highest increase for IgA (2.07-fold). Peak IgG levels against 27 antigens, including the antigen SA0688, were significantly elevated in bacteremia patients versus controls (P≤0.05). Expression of diverse genes, including SA0688, was ubiquitously high in both isolates at all time points during incubation in blood. However, only a limited number of genes were specifically up- or downregulated in both isolates when cultured in blood, compared to the start of incubation in blood or during incubation in BHI broth. In conclusion, most staphylococcal antigens tested in this study, including many known virulence factors, do not induce uniform increases in the antibody levels in bacteremia patients. In addition, the expression of these antigens by S. aureus is not significantly altered by incubation in human blood over time. One immunogenic and ubiquitously expressed antigen is the putative iron-regulated ABC transporter SA0688.

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Association of variants in selected genes mediating host immune response with duration of Staphylococcus aureus bacteremia.

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