Anti-staphylococcal humoral immune response in persistent nasal carriers and noncarriers of Staphylococcus aureus

BACKGROUND. Persistent carriers have a higher risk of Staphylococcus aureus infections than noncarriers but a lower risk of bacteremia-related death. Here, the role played by anti-staphylococcal antibodies was studied. METHODS. Serum samples from 15 persistent carriers and 19 noncarriers were analyzed for immunoglobulin (Ig) G, IgA, and IgM binding to 19 S. aureus antigens, by means of Luminex technology. Nasal secretions and serum samples obtained after 6 months were also analyzed. RESULTS. Median serum IgG levels were significantly higher in persistent carriers than in noncarriers for toxic shock syndrome toxin (TSST)-1 (median fluorescence intensity [MFI] value, 11,554 vs. 4291; P < .001) and staphylococcal enterotoxin (SE) A (742 vs. 218; P < .05); median IgA levels were higher for TSST-1 (P < .01), SEA, and clumping factor (Clf) A and B (P < .05). The in vitro neutralizing capacity of anti-TSST-1 antibodies was correlated with the MFI value (R(2) = 0.93) and was higher in persistent carriers (90.6% vs. 70.6%; P < .05). Antibody levels were stable over time and correlated with levels in nasal secretions (for IgG, R(2) = 0.87; for IgA, R(2) = 0.77). CONCLUSIONS. Antibodies to TSST-1 ha

Characterization of a Mouse-Adapted <i>Staphylococcus aureus</i> Strain

<div><p>More effective antibiotics and a protective vaccine are desperately needed to combat the ‘superbug’ <i>Staphylococcus aureus.</i> While in vivo pathogenicity studies routinely involve infection of mice with human <i>S. aureus</i> isolates, recent genetic studies have demonstrated that <i>S. aureus</i> lineages are largely host-specific. The use of such animal-adapted <i>S. aureus</i> strains may therefore be a promising approach for developing more clinically relevant animal infection models. We have isolated a mouse-adapted <i>S. aureus</i> strain (JSNZ) which caused a severe outbreak of preputial gland abscesses among male C57BL/6J mice. We aimed to extensively characterize this strain on a genomic level and determine its virulence potential in murine colonization and infection models. JSNZ belongs to the MLST type ST88, rare among human isolates, and lacks an <i>hlb</i>-converting phage encoding human-specific immune evasion factors. Naive mice were found to be more susceptible to nasal and gastrointestinal colonization with JSNZ than with the human-derived Newman strain. Furthermore, naïve mice required antibiotic pre-treatment to become colonized with Newman. In contrast, JSNZ was able to colonize mice in the absence of antibiotic treatment suggesting that this strain can compete with the natural flora for space and nutrients. In a renal abscess model, JSNZ caused more severe disease than Newman with greater weight loss and bacterial burden. In contrast to most other clinical isolates, JSNZ can also be readily genetically modified by phage transduction and electroporation. In conclusion, the mouse-adapted strain JSNZ may represent a valuable tool for studying aspects of mucosal colonization and for screening novel vaccines and therapies directed at preventing colonization.</p></div

DNA microarray analysis of JSNZ and human CC88 isolates.

<p>DNA microarray analysis of JSNZ and human CC88 isolates.</p

JSNZ efficiently colonizes the nose and gastrointestinal tract of CD1 mice.

<p>Female CD1 mice were intranasally inoculated with 10⁸ CFUs <i>S. aureus</i> JSNZ Sm^R and Newman Sm^R. Mice were pre-treated with Sm to reduce the natural flora (filled symbols) or left untreated (empty symbols). Bacterial loads in the nose (A) and feces (B) were determined at indicated time points and the median is shown. Data were compared using a two-tailed Mann Whitney test (A, p = 0.0338 for Sm-treated JSNZ <i>versus</i> Newman and p = 0.0168 for Sm-untreated JSNZ <i>versus</i> Newman) or a Friedman test followed by Dunn's correction for multiple comparisons (B, p = 0.0455 for Sm-treated JSNZ <i>versus</i> Newman and p = 0.0003 for Sm-untreated JSNZ <i>versus</i> Newman). Culture negative samples were plotted at the detection limit (dashed line). One representative experiment out of two is shown.</p