title: Combining in vitro protein detection and in vivo antibody detection identifies potential vaccine targets against Staphylococcus aureus during osteomyelitis.
abstract: Currently, little is known about the in vivo human immune response against Staphylococcus aureus during a biofilm-associated infection, such as osteomyelitis, and how this relates to protein production in biofilms in vitro. Therefore, we characterized IgG responses in 10 patients with chronic osteomyelitis against 50 proteins of S. aureus, analyzed the presence of these proteins in biofilms of the infecting isolates on polystyrene (PS) and human bone in vitro, and explored the relation between in vivo and in vitro data. IgG levels against 15 different proteins were significantly increased in patients compared to healthy controls. Using a novel competitive Luminex-based assay, eight of these proteins [alpha toxin, Staphylococcus aureus formyl peptide receptor-like 1 inhibitor (FlipR), glucosaminidase, iron-responsive surface determinants A and H, the putative ABC transporter SACOL0688, staphylococcal complement inhibitor (SCIN), and serine-aspartate repeat-containing protein E (SdrE)] were also detected in a majority of the infecting isolates during biofilm formation in vitro. However, 4 other proteins were detected in only a minority of isolates in vitro while, vice versa, 7 proteins were detected in multiple isolates in vitro but not associated with significantly increased IgG levels in patients. Detection of proteins was largely confirmed using a transcriptomic approach. Our data provide further insights into potential therapeutic targets, such as for vaccination, to reduce S. aureus virulence and biofilm formation. At the same time, our data suggest that either in vitro or immunological in vivo data alone should be interpreted cautiously and that combined studies are necessary to identify potential targets.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. p.denreijer@erasmusmc.nl.
authors.forename: P Martijn
authors.initials: PM
authors.lastname: den Reijer
authors.affiliation: Department of Orthopaedics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marjan
authors.initials: M
authors.lastname: Sandker
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Snijders
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Mehri
authors.initials: M
authors.lastname: Tavakol
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Antoni P A
authors.initials: AP
authors.lastname: Hendrickx
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Willem J B
authors.initials: WJ
authors.lastname: van Wamel
mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000032:analysis*; D018441:Biofilms / Q000254:growth & development*; D002908:Chronic Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000473:pathology*; D013203:Staphylococcal Infections / Q000473:pathology*; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology* / Q000502:physiology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D013209:Staphylococcal Vaccines
keywords: Biofilm; Luminex; Osteomyelitis; Staphylococcus aureus; Virulence factors