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DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?

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Abstract

Providing evidence for microbial genetic determinants’ impact on outcome in Staphylococcus aureus bloodstream infections (SABSI) is challenging due to the complex and dynamic microbe–host interaction. Our recent population-based prospective study reported an association between the S. aureus clonal complex (CC) 30 genotype and mortality in SABSI patients. This follow-up investigation aimed to examine the genetic profiles of the SABSI isolates and test the hypothesis that specific genetic characteristics in S. aureus are associated with mortality. SABSI isolates (n = 305) and S. aureus CC30 isolates from asymptomatic nasal carriers (n = 38) were characterised by DNA microarray analysis and spa typing. Fisher’s exact test, least absolute shrinkage and selection operator (LASSO) and elastic net regressions were performed to discern within four groups defined by patient outcome and characteristics. No specific S. aureus genetic determinants were found to be associated with mortality in SABSI patients. By applying LASSO and elastic net regressions, we found evidence suggesting that agrIII and cna were positively and setC (=selX) and seh were negatively associated with S. aureus CC30 versus non-CC30 isolates. The genes chp and sak, encoding immune evasion molecules, were found in higher frequencies in CC30 SABSI isolates compared to CC30 carrier isolates, indicating a higher virulence potential. In conclusion, no specific S. aureus genes were found to be associated with mortality by DNA microarray analysis and state-of-the-art statistical analyses. The next natural step is to test the hypothesis in larger samples with higher resolution methods, like whole genome sequencing.

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Acknowledgements

We thank Inge Skråmm, Hanne G. M. Hexeberg and co-workers from the Department of Orthopaedics for the data and sample collection from elective surgery patients. We thank colleagues in the Department of Microbiology and Infection Control for the diagnostics of S. aureus isolates and Karin Helmersen for performing the spa typing. We are grateful for the technical assistance from Antje Ruppelt, Medical Faculty Carl Gustav Carus, Dresden, Germany, regarding the microarray analyses.

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Authors and Affiliations

  1. Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway

    A. Blomfeldt, H. V. Aamot & T. M. Leegaard

  2. Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital and University of Oslo, Lørenskog, Norway

    H. V. Aamot

  3. Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway

    A. N. Eskesen

  4. Alere Technologies GmbH, Jena, Germany

    S. Monecke

  5. Institute for Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany

    S. Monecke

  6. Department of Infectious Diseases Epidemiology, Norwegian Institute of Public Health, Oslo, Norway

    R. A. White & J. V. Bjørnholt

  7. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    T. M. Leegaard

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  1. A. Blomfeldt
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  2. H. V. Aamot
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  7. J. V. Bjørnholt
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Correspondence to A. Blomfeldt.

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Conflict of interest

The authors declare that they have no conflicts of interest. S. Monecke is an employee at Alere Technologies GmbH, Jena, Germany.

Funding

The study was supported by a Strategic Research grant (2619028/90003) from Akershus University Hospital.

Ethical considerations

Ethical approval was given by the Norwegian Regional Ethics Committee South-East (2009/2149-1) and by the Data Protection Official at Akershus University Hospital (2010-041).

Informed consent

Written informed consent was obtained from all individual participants included in the study, except for a small fraction of patients (n = 22) who died before an interview could be performed and consent could be asked for.

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Blomfeldt, A., Aamot, H.V., Eskesen, A.N. et al. DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?. Eur J Clin Microbiol Infect Dis 35, 1285–1295 (2016). https://doi.org/10.1007/s10096-016-2663-3

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