Abstract

Staphylococcus aureus bacteremia (SAB) is associated with high morbidity and mortality, which varies depending on the source of infection. Nevertheless, the global molecular epidemiology of SAB and its possible association with specific virulence factors remains unclear. Using DNA microarrays, a total of 833 S. aureus strains (785 SAB and 48 colonizing strains) collected in Spain over a period of 15 years (2002–2017) were characterized to determine clonal complex (CC), agr type and repertoire of resistance and virulence genes in order to provide an epidemiological overview of CCs causing bloodstream infection, and to analyze possible associations between virulence genes and the most common sources of bacteremia. The results were also analyzed by acquisition (healthcare-associated [HA] and community-acquired [CA]), methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains, and patient age (adults vs. children). Our results revealed high clonal diversity among SAB strains with up to 28 different CCs. The most prevalent CCs were CC5 (30.8%), CC30 (20.3%), CC45 (8.3%), CC8 (8.4%), CC15 (7.5%), and CC22 (5.9%), which together accounted for 80% of all cases. A higher proportion of CC5 was found among HA strains than CA strains (35.6 vs. 20.2%, p < 0.001). CC5 was associated with methicillin resistance (14.7 vs. 79.4%, p < 0.001), whereas CC30, CC45, and CC15 were correlated with MSSA strains (p < 0.001). Pathogen-related molecular markers significantly associated with a specific source of bacteremia included the presence of sea, undisrupted hlb and isaB genes with catheter-related bacteremia; sed, splE, and fib genes with endocarditis; undisrupted hlb with skin and soft tissue infections; and finally, CC5, msrA resistance gene and hla gene with osteoarticular source. Our study suggests an association between S. aureus genotype and place of acquisition, methicillin resistance and sources of bloodstream infection, and provides a valuable starting point for further research insights into intrinsic pathogenic mechanisms involved in the development of SAB.

Highlights

  • Staphylococcus aureus is an opportunistic pathogen that can potentially cause a wide range of infections

  • A comparison of the two groups revealed that only CC5 was associated with methicillin resistance (14.7 vs. 79.4%, p < 0.001), whereas CC30, CC45 and CC15 were correlated with MSSA strains (p < 0.001; Table 2)

  • The present study describes and gives a global epidemiological overview of the molecular epidemiology of a large collection of S. aureus strains focused on bloodstream infections in Spain over a 15-years period

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Summary

Introduction

Staphylococcus aureus is an opportunistic pathogen that can potentially cause a wide range of infections It is a leading cause of bacteremia and represents a significant global health problem (Weiner et al, 2016). The overall mortality rate from SAB varies depending on the primary focus of infection (the highest rates occur in patients with infective endocarditis and pulmonary infections, and the lowest in patients with catheter-related infections) and on the complications deriving from SAB. This association makes it necessary to regard SAB not as a single entity, but as a heterogeneous group of infections that can evolve differently and require source-specific management (van Hal et al, 2012). Determining the role of particular genetic backgrounds (clonality and virulence) in bloodstream infections caused by S. aureus has become a real challenge due to the diversity, redundancy and host specificity of the virulence factors

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