title: DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality?
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.
authors.affiliation: Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway. anita.blomfeldt@ahus.no.
authors.forename: A
authors.initials: A
authors.lastname: Blomfeldt
authors.affiliation: Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway.|Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital and University of Oslo, Lørenskog, Norway.
authors.forename: H V
authors.initials: HV
authors.lastname: Aamot
authors.affiliation: Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway.
authors.forename: A N
authors.initials: AN
authors.lastname: Eskesen
authors.affiliation: Alere Technologies GmbH, Jena, Germany.|Institute for Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Monecke
authors.affiliation: Department of Infectious Diseases Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: R A
authors.initials: RA
authors.lastname: White
authors.affiliation: Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: T M
authors.initials: TM
authors.lastname: Leegaard
authors.affiliation: Department of Infectious Diseases Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: J V
authors.initials: JV
authors.lastname: Bjørnholt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000382:microbiology / Q000401:mortality; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000382:microbiology / Q000401:mortality; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity
chemical_list: D004269:DNA, Bacterial