Familial Clustering of<i>Staphylococcus aureus</i>Bacteremia in First-Degree Relatives

Oestergaard, Louise Bruun; Christiansen, M.; Schmiegelow, Michelle; Skov, Robert; Andersen, Paal Skytt; Petersen, Andreas; Aasbjerg, Kristian; Gerds, Thomas Alexander; Andersen, Per Kragh; Torp‐Pedersen, Christian

doi:10.7326/m15-2762

Cited by 15 publications

(11 citation statements)

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“…12, 13 Although a twin study failed to demonstrate an association between nasal carriage of monozygotic twin status, 30 a recent 20-year nationwide cohort study drawing from the entire Danish population of >8 million individuals showed evidence of familial clustering of SAB in first-degree relatives. 6 Among the 34 774 individuals with a first-degree relative (index case patient) previously hospitalized with SAB who were followed for a mean of 7.8 years, a higher rate of SAB was observed among first-degree relatives than among the background Danish population (standardized incidence ratio (SIR): 2.49; (95% confidence interval (CI): 1.95–3.19)). This estimate was significantly higher if the index case patient was a sibling (SIR: 5.01; (95% CI: 3.30–7.62) than a parent and highest in siblings of individuals who developed non-hospital acquired SAB (SIR: 5.66; (95% CI: 3.47–9.24)).…”

Section: Discussionmentioning

confidence: 99%

“…5 In humans, first-degree relatives of patients previously hospitalized with S. aureus bacteremia (SAB) were themselves significantly more likely to develop SAB than the population as a whole. 6 Our recent genome-wide study of >50 000 white subjects found that two single-nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) class II region on chromosome 6 were associated with susceptibility to S. aureus infection at a genome-wide significant level. 7 …”

Section: Introductionmentioning

confidence: 99%

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Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping

Cyr

Allen

Du³

et al. 2017

Genes Immun

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The incidence of Staphylococcus aureus bacteremia (SAB) is significantly higher in African American (AA) than in European-descended populations. We used admixture mapping (AM) to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to SAB in AAs. A total of 565 adult AAs (390 cases with SAB; 175 age-matched controls) were genotyped for AM analysis. A case-only admixture score and a mixed χ2(1df) score (MIX) to jointly evaluate both single-nucleotide polymorphism (SNP) and admixture association (P<5.00e-08) were computed using MIXSCORE. In addition, a permutation scheme was implemented to derive multiplicity adjusted P-values (genome-wide 0.05 significance threshold: P<9.46e-05). After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P=4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping

Cyr

Allen

Du³

et al. 2017

Genes Immun

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“…Transition from carriage to bloodstream infection and further on to IE may thus rather be due to host genetics and host immune responses than caused by specific traits of the infecting bacterium. In support of this, we have recently reported a higher incidence of S. aureus bacteraemia among first degree relatives of S. aureus patients compared to the general population, suggesting that there is a host genetic component, partly explaining why some individuals are more prone to acquire S. aureus bacteraemia than others [ 44 ]. Specific host gene variants have also been associated to susceptibility to endocarditis [ 45–48 ].…”

Section: Discussionmentioning

confidence: 86%

Whole-genome sequencing of bloodstream Staphylococcus aureus isolates does not distinguish bacteraemia from endocarditis

et al. 2017

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Most Staphylococcus aureus isolates can cause invasive disease given the right circumstances, but it is unknown if some isolates are more likely to cause severe infections than others. S. aureus bloodstream isolates from 120 patients with definite infective endocarditis and 121 with S. aureus bacteraemia without infective endocarditis underwent whole-genome sequencing. Genome-wide association analysis was performed using a variety of bioinformatics approaches including SNP analysis, accessory genome analysis and k-mer based analysis. Core and accessory genome analyses found no association with either of the two clinical groups. In this study, the genome sequences of S. aureus bloodstream isolates did not discriminate between bacteraemia and infective endocarditis. Based on our study and the current literature, it is not convincing that a specific S. aureus genotype is clearly associated to infective endocarditis in patients with S. aureus bacteraemia.

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“…A growing body of evidence suggests that human genetic variability may influence the risk for and severity of S. aureus infections, including complicated SAB and IE. Evidence supporting a genetic basis for susceptibility to SAB includes: i) higher rates of S. aureus infections in distinct ethnic populations (52–56); ii) familial clusters of S. aureus infection (57–60); iii) rare genetic conditions causing susceptibility to S. aureus (61–66); and iv) variable susceptibility to S. aureus in inbred mice (67–71) and cattle (72,73). The first GWAS evidence of human genetic susceptibility to S. aureus infection by comparing 4,701 cases of S. aureus infection and 45,344 matched controls was presented (74).…”

Section: Discussionmentioning

confidence: 99%

All Staphylococcus aureus bacteraemia strains have the potential to cause infective endocarditis: results of GWAS and experimental animal studies

Bastien

Meyers

Salgado-Pabón

et al. 2022

Preprint

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and KeywordsAimsInfective endocarditis (IE) complicates 10-20% of Staphylococcus aureus bacteraemia (SAB). We aimed to determine whether IE strains of S. aureus are genotypically different or behave differently in experimental endocarditis models as compared to non-IE SAB strains.Methods and ResultsWe conducted a genome wide association study (GWAS) of 924 S. aureus genomes from IE (274) and non-IE (650) SAB patients, and tested a subset of strains in two experimental animal models of IE, one studying the early step of bacterial adhesion to inflamed mice valves, the second evaluating the local and systemic developmental process of IE on mechanically damaged rabbit valves. The genetic profile of S. aureus IE and non-IE SAB strains did not differ when considering single nucleotide polymorphisms, coding sequences and k-mers analyses in GWASs. In the inflammation-induced IE model in mice no difference was observed between IE and non-IE SAB strains both in adhesion to the cardiac valves and in the propensity to cause IE; in the mechanical IE-induced rabbit model, there was no difference between IE and non-IE SAB strains regarding vegetation size and CFU.ConclusionS. aureus isolates from SAB patients with and without IE were indistinguishable, by GWAS and by two in vivo models of IE. Thus, S. aureus strain variation is not the primary determinant of IE. Pending the possible identification of host factors predisposing to IE, all strains of S. aureus must be considered in patients as capable of causing this common, lethal infection once they have accessed the bloodstream.Translational PerspectiveStaphylococcus aureus endocarditis (IE) is a deadly complication of S. aureus bacteraemia (SAB). Beyond well-identified host related IE risk factors, whether bacterial features may influence the occurrence of IE in the course of bacteraemia remain elusive. We analysed the genomes of 924 S. aureus strains from IE and non-IE SAB and compared some in two in vivo IE models. We demonstrated that the propensity of S. aureus to cause IE in the course of bacteraemia does not depend on the intrinsic genetic or virulence factors of S. aureus. These findings are of importance for the management of S. aureus bacteraemia.

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Familial Clustering ofStaphylococcus aureusBacteremia in First-Degree Relatives

Abstract: The Danish Heart Foundation and the Christian Larsen and Judge Ellen Larsen Foundation.

Cited by 15 publications

References 40 publications

Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping

Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping

Whole-genome sequencing of bloodstream Staphylococcus aureus isolates does not distinguish bacteraemia from endocarditis

All Staphylococcus aureus bacteraemia strains have the potential to cause infective endocarditis: results of GWAS and experimental animal studies

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