Vaccination with SesC Decreases Staphylococcus epidermidis Biofilm Formation

Shahrooei, Mohammad; Hira, Vishal; Khodaparast, Laleh; Stijlemans, Benoı̂t; Kucharíková, Soňa; Burghout, Peter; Hermans, Peter W. M.; Eldere, Johan Van

doi:10.1128/iai.00104-12

Cited by 58 publications

(60 citation statements)

References 42 publications

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“…The fluorescent reporter was then used to compare PhnD antibodies to those for other targets, including several proteins with a known role in S. epidermidis biofilm formation: EmbP (SERP1011), Aap (SERP2398), and SesC (SERP2264) (17)(18)(19)(20). Treatment with EmbP antibodies also led to a large decrease in biofilm formation (91% reduction versus the control); however, none of the other antibodies showed substantial effects at the endpoint (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Antibodies to PhnD Inhibit Staphylococcal Biofilms

et al. 2014

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Biofilm formation on central lines or peripheral catheters is a serious threat to patient well-being. Contaminated vascular devices can act as a nidus for bloodstream infection and systemic pathogen dissemination. Staphylococcal biofilms are the most common cause of central-line-associated bloodstream infections, and antibiotic resistance makes them difficult to treat. As an alternative to antibiotic intervention, we sought to identify anti-staphylococcal biofilm targets for the development of a vaccine or antibody prophylactic. A screening strategy was devised using a microfluidic system to test antibody-mediated biofilm inhibition under biologically relevant conditions of shear flow. Affinity-purified polyclonal antibodies to target antigen PhnD inhibited both Staphylococcus epidermidis and S. aureus biofilms. PhnD-specific antibodies blocked biofilm development at the initial attachment and aggregation stages, and deletion of phnD inhibited normal biofilm formation. We further adapted our microfluidic biofilm system to monitor the interaction of human neutrophils with staphylococcal biofilms and demonstrated that PhnD-specific antibodies also serve as opsonins to enhance neutrophil binding, motility, and biofilm engulfment. These data support the identification of PhnD as a lead target for biofilm intervention strategies performed either by vaccination or through passive administration of antibodies.

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Section: Resultsmentioning

confidence: 99%

“…Given that all targets in Fig. 3 and 4 are surface exposed (18,19,26,27), it is clear that biofilm inhibition requires more than just antibody binding to the cell surface. In fact, abundant antibody binding to highly expressed surface antigens may induce cell aggregation and increase biofilm formation, as observed for Aap ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to PhnD Inhibit Staphylococcal Biofilms

et al. 2014

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“…S. aureus 132 grown under planktonic or biofilm conditions was preincubated with preimmune serum, 1% or 10% BME-specific sera, or PBS as a control. After incubation, bacteria were mixed with whole blood for 30 min (45). Staphylococcal killing was monitored by spreading sample aliquots on TSA agar medium followed by colony formation and enumeration.…”

Section: Resultsmentioning

confidence: 99%

“…The opsonophagocytosis and killing assay was previously described (45). Briefly, 1 ml of a planktonic culture of strain S. aureus 132 grown overnight was pelleted for 5 min at 12,000 ϫ g at 4°C, washed twice with PBS, and subsequently diluted to an OD 600 of 0.5.…”

Section: Ethics Statementmentioning

confidence: 99%

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

et al. 2014

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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.

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“…S. epidermidis RP62A expresses 11 proteins containing an LPXTG motif (10). Of these, the accumulation-associated protein (Aap) (11,12), the fibrinogen binding protein (SdrG) (13)(14)(15), the collagen binding protein (SdrF) (16), the Bap homologue protein (Bhp) (17), and S. epidermidis surface protein C (SesC) (18,19) have all been implicated in the biofilm phenotype of S. epidermidis. Aap was previously shown to be essential for the accumulation of S. epidermidis RP62A on polymer surfaces (11).…”

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Role for the A Domain of Unprocessed Accumulation-Associated Protein (Aap) in the Attachment Phase of the Staphylococcus epidermidis Biofilm Phenotype

et al. 2014

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e The polysaccharide intercellular adhesin or the cell wall-anchored accumulation-associated protein (Aap) mediates cellular accumulation during Staphylococcus epidermidis biofilm maturation. Mutation of sortase, which anchors up to 11 proteins (including Aap) to the cell wall, blocked biofilm development by the cerebrospinal fluid isolate CSF41498. Aap was implicated in this phenotype when Western blots and two-dimensional (2D) electrophoresis revealed increased levels of the protein in culture supernatants. Unexpectedly, reduced levels of primary attachment were associated with impaired biofilm formation by CSF41498 srtA and aap mutants. In contrast to previous studies, which implicated Aap proteolytic cleavage and, specifically, the Aap B domains in biofilm accumulation, the CSF41498 Aap protein was unprocessed. Furthermore, aap appeared to play a less important role in the biofilm phenotype of S. epidermidis 1457, in which the Aap protein is processed. Anti-Aap A-domain IgG inhibited primary attachment and biofilm formation in strain CSF41498 but not in strain 1457. The nucleotide sequences of the aap gene A-domain region and cleavage site in strains CSF41498 and 1457 were identical, implicating altered protease activity in the differential Aap processing results in the two strains. These data reveal a new role for the A domain of unprocessed Aap in the attachment phase of biofilm formation and suggest that extracellular protease activity can influence whether Aap contributes to the attachment or accumulation phases of the S. epidermidis biofilm phenotype.

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Vaccination with SesC Decreases Staphylococcus epidermidis Biofilm Formation

Cited by 58 publications

References 42 publications

Antibodies to PhnD Inhibit Staphylococcal Biofilms

Antibodies to PhnD Inhibit Staphylococcal Biofilms

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

Role for the A Domain of Unprocessed Accumulation-Associated Protein (Aap) in the Attachment Phase of the Staphylococcus epidermidis Biofilm Phenotype

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