Immunogenicity of toxins during Staphylococcus aureus infection

AB - BACKGROUND: Toxins are important Staphylococcus aureus virulence factors, but little is known about their immunogenicity during infection. Here, additional insight is generated. METHODS: Serum samples from 206 S. aureus-infected patients and 201 hospital-admitted control subjects were analyzed for immunoglobulin (Ig) G binding to 20 toxins, using flow-cytometry based technology. Antibody levels were associated with p

Natural Variability of In Vitro Adherence to Fibrinogen and Fibronectin Does Not Correlate with In Vivo Infectivity of Staphylococcus aureus▿

Adherence to fibrinogen and fibronectin plays a crucial role in Staphylococcus aureus experimental endocarditis. Previous genetic studies have shown that infection and carriage isolates do not systematically differ in their virulence-related genes, including genes conferring adherence, such as clfA and fnbA. We set out to determine the range of adherence phenotypes in carriage isolates of S. aureus, to compare the adherence of these isolates to the adherence of infection isolates, and to determine the relationship between adherence and infectivity in a rat model of experimental endocarditis. A total of 133 healthy carriage isolates were screened for in vitro adherence to fibrinogen and fibronectin, and 30 isolates were randomly chosen for further investigation. These 30 isolates were compared to 30 infective endocarditis isolates and 30 blood culture isolates. The infectivities of the carriage isolates, which displayed either extremely low or high adherence to fibrinogen and fibronectin, were tested using a rat model of experimental endocarditis. The levels of adherence to both fibrinogen and fibronectin were very similar for isolates from healthy carriers and members of the two groups of infection isolates. All three groups of isolates showed a wide range of adherence to fibrinogen and fibronectin. Moreover, the carriage isolates that showed minimal adherence and the carriage isolates that showed strong adherence had the same infectivity in experimental endocarditis. Adherence was proven to be important for pathogenesis in experimental endocarditis, but even the least adherent carriage strains had the ability to induce infection. We discuss the roles of differential gene expression, human host factors, and gene redundancy in resolving this apparent paradox

Delta Hemolysin and Phenol-Soluble Modulins, but Not Alpha Hemolysin or Panton-Valentine Leukocidin, Induce Mast Cell Activation

International audienceMast cells are located at host interfaces, such as the skin, and contribute to the first-line defense against pathogens by releasing soluble mediators, including those that induce itching and scratching behavior. Here, we show that delta-hemolysin (Hld) and phenol soluble modulins (PSMs) PSMα1 and PSMα3, but not alpha-hemolysin (Hla) or Panton-Valentine leukocidin (PVL), induce dose-dependent tryptase, and lactate dehydrogenase (LDH) release by the HMC-1 human mast cell line. Using supernatants from isogenic strains, we verified that tryptase and LDH release was Hld- and PSMα-dependent. PSMα1 and Hld production was detected in 65 and 17% of human Staphylococcus aureus-infected skin abscess specimens, respectively, but they were produced in vitro by all clinical isolates. The results suggest that Hld and PSM-α1 produced in vivo during S. aureus skin infections induce the release of mast cell mediators responsible for itching and scratching behavior, which may enhance skin to skin transmission of S. aureus via the hands. As Hld and PSMs are upregulated by accessory gene regulator (agr), their association may contribute to the elective transmission of S. aureus strains with a functional agr system

The levels of antibodies to Panton-Valentine leukocidin (PVL) vary with PVL prevalence along a north-to-south gradient

International audienceRecent research on Staphylococcus aureus vaccine development has focused on active immunization against Panton-Valentine leukocidin (PVL), a potent leukotoxin associated with both superficial and severe deep-seated infections. PVL prevalence is highly variable worldwide, but it is unknown to what extent immunity to PVL varies between patients from geographic areas with different PVL-positive S. aureus prevalences. We conducted a retrospective multicentric study of anti-PVL and anti-alpha-toxin (Hla) antibody levels in uninfected adult patients from France (low PVL prevalence; n = 200), Algeria (moderate prevalence; n = 143), and Senegal (high prevalence; n = 228). The antibody levels were quantified by an enzyme-linked immunosorbent assay (ELISA) procedure. Because Hla is present in virtually all S. aureus strains, its corresponding antibody levels were considered to reflect population exposure to S. aureus. Compared with French participants, the average anti-PVL antibody levels were 2.5-fold and 8.2-fold higher in Algerian and Senegalese participants, respectively (p \textless 0.001). Conversely, anti-Hla antibody levels did not differ between participants from the three countries, suggesting that the observed differences in anti-PVL antibody levels were not biased by variations in population exposure to S. aureus. Hence, anti-PVL antibody levels in the general populations of France, Algeria, and Senegal vary widely and match variations in PVL-positive S. aureus strain prevalence, with an increasing north-to-south gradient. To conclude, immunity to PVL in a given population correlates with local PVL prevalence. This finding can help to inform PVL vaccine strategies