Abstract
Attempts to develop an efficient anti-staphylococcal vaccine in humans have so far been unsuccessful. Therefore, more knowledge of the antigens that are expressed by Staphylococcus aureus in human blood and induce an immune response in patients is required. In this study we further characterize the serial levels of IgG and IgA antibodies against 56 staphylococcal antigens in multiple serum samples of 21 patients with a S. aureus bacteremia, compare peak IgG levels between patients and 30 non-infected controls, and analyze the expression of 3626 genes by two genetically distinct isolates in human blood. The serum antibody levels were measured using a bead-based flow cytometry technique (xMAP®, Luminex corporation). Gene expression levels were analyzed using a microarray (BµG@s microarray). The initial levels and time taken to reach peak IgG and IgA antibody levels were heterogeneous in bacteremia patients. The antigen SA0688 was associated with the highest median initial-to-peak antibody fold-increase for IgG (5.05-fold) and the second highest increase for IgA (2.07-fold). Peak IgG levels against 27 antigens, including the antigen SA0688, were significantly elevated in bacteremia patients versus controls (P≤0.05). Expression of diverse genes, including SA0688, was ubiquitously high in both isolates at all time points during incubation in blood. However, only a limited number of genes were specifically up- or downregulated in both isolates when cultured in blood, compared to the start of incubation in blood or during incubation in BHI broth. In conclusion, most staphylococcal antigens tested in this study, including many known virulence factors, do not induce uniform increases in the antibody levels in bacteremia patients. In addition, the expression of these antigens by S. aureus is not significantly altered by incubation in human blood over time. One immunogenic and ubiquitously expressed antigen is the putative iron-regulated ABC transporter SA0688.
Highlights
Staphylococcus aureus is one of the most common causes of bloodstream infections [1,2] and S. aureus bloodstream infections are associated with serious complications such as infective endocarditis and prosthetic device infection [3,4,5]
pulsed-field gel electrophoresis (PFGE) analysis was performed on the first available S. aureus isolates from all 21 bacteremia patients
In this study we investigated the humoral immune response against 56 staphylococcal antigens in bacteremia patients
Summary
Staphylococcus aureus is one of the most common causes of bloodstream infections [1,2] and S. aureus bloodstream infections are associated with serious complications such as infective endocarditis and prosthetic device infection [3,4,5]. Due to the increasing antibiotic resistance of clinical S. aureus isolates [9,10] and the simultaneous decrease in the number of newly approved antimicrobial agents [11,12], the treatment of S. aureus bacteremia is becoming increasingly difficult. One potential strategy is the development of a vaccine. Despite the promising results of anti-staphylococcal vaccines in animal models, efforts to develop an efficient vaccine against S. aureus in humans have so far failed [13,14,15]
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