Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

Abstract

The Staphylococcus aureus biofilm mode of growth is associated with several chronic infections that are very difficult to treat due to the recalcitrant nature of biofilms to clearance by antimicrobials. Accordingly, there is an increasing interest in preventing the formation of S. aureus biofilms and developing efficient antibiofilm vaccines. Given the fact that during a biofilm-associated infection, the first primary interface between the host and the bacteria is the self-produced extracellular matrix, in this study we analyzed the potential of extracellular proteins found in the biofilm matrix to induce a protective immune response against S. aureus infections. By using proteomic approaches, we characterized the exoproteomes of exopolysaccharide-based and proteinbased biofilm matrices produced by two clinical S. aureus strains. Remarkably, results showed that independently of the nature of the biofilm matrix, a common core of secreted proteins is contained in both types of exoproteomes. Intradermal administration of an exoproteome extract of an exopolysaccharide-dependent biofilm induced a humoral immune response and elicited the production of interleukin 10 (IL-10) and IL-17 in mice. Antibodies against such an extract promoted opsonophagocytosis and killing of S. aureus. Immunization with the biofilm matrix exoproteome significantly reduced the number of bacterial cells inside a biofilm and on the surrounding tissue, using an in vivo model of mesh-associated biofilm infection. Furthermore, immunized mice also showed limited organ colonization by bacteria released from the matrix at the dispersive stage of the biofilm cycle. Altogether, these data illustrate the potential of biofilm matrix exoproteins as a promising candidate multivalent vaccine against S. aureus biofilm-associated infections.

Comparative studies of the immunogenicity and protective potential of biofilmvsplanktonicStaphylococcus aureusvaccine against bovine mastitis using non-invasive mouse mastitis as a model system

“…aureus is frequently associated with formation of biofilm in the mammary gland, making antibiotic therapy of bovine mastitis difficult (Melchior et al 2006). Microorganisms residing in biofilm respond poorly to antimicrobial agents and resist host innate immune mechanisms (Thurlow et al 2011;Zecconi & Scali 2013;Gil et al 2014). Upon entry into the mammary gland, S. aureus attaches to the epithelial lining of the mammary gland using specific receptors and begins the process of colonization.…”

“…Maira-Litran et al 2005;Prenafeta et al 2010;Skurnik et al 2010;Gil et al 2014). Use of the slime-associated antigenic complex (SAAC) of S. aureus has been reported to protect against localized and systemic infections of S. aureus in mice(Cywes-Bentley et al 2013) but failed to protect against intramammary infections in cows, only leading to a reduction in the multiplication of S. aureus in the mammary gland(Prenafeta et al 2010) Maira-Litran et al (2005).…”

Comparison of the Antibiotic Activities of Daptomycin, Vancomycin, and the Investigational Fluoroquinolone Delafloxacin against Biofilms from Staphylococcus aureus Clinical Isolates

“…With respect to matrix composition, S. aureus biofilms consist mainly of polysaccharides (poly-N-acetylglucosamine and teichoic acid), extracellular matrix proteins, and DNA released from bacteria (30)(31)(32)(33), but the relative amounts of these components may differ among the biofilms formed from different strains due to differences in the expression of the genes regulating biofilm formation (32,34). The matrix composition of the biofilms formed by the strains used in our study is not known, but we observed major differences in the capacities of the strains to form biofilms.…”

Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics

“…In that study, two different antigens were used: SERP0630 (MenD) (for S. epidermidis) and SACOL1138, or iron-regulated surface determinant B (IsdB) (for S. aureus). With S. aureus, a recent study reported that extracellular proteins found in the biofilm matrix could induce a protective immune response that prevented subsequent infections (322).…”