Development of a rat central venous catheter model for evaluation of vaccines to prevent<i>Staphylococcus epidermidis</i>and<i>Staphylococcus aureus</i>early biofilms

Ebert, Tim; Smith, Sharon; Pancari, Greg; Wu, Xiongfei; Zorman, Julie; Clark, Desmond; Cook, J L; Burns, Carol; Antonello, Joseph; Cope, Leslie D.; Nagy, Eszter; Meinke, Andreas; McNeely, Tessie

doi:10.4161/hv.7.6.15407

Cited by 16 publications

(10 citation statements)

References 39 publications

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“…In validating our model, we found that rats required immunosuppression and a high inoculum, consistent with previous reports (76,77,88,89). Following validation, we used the model to assess virulence of the mutant S. epidermidis strains 3 days postinfection.…”

Section: Figsupporting

confidence: 64%

“…***, P Ͻ 0.001; **, P Ͻ 0.01; *, P Ͻ 0.05 (n Ն 4 biological replicates). inocula of S. epidermidis from the bloodstream in the absence of a foreign body (76,77), to increase the percentage of catheters seeded following S. epidermidis challenge, rats were given intraperitoneal injections of CP to produce leukopenia. To validate our model and confirm that the presence of a catheter and immunosuppression are critical for S. epidermidis infection, rats were divided into four groups prior to bacterial inoculation: (i) catheter plus CP, (ii) catheter only, (iii) CP only, and (iv) no catheter or CP (no treatment).…”

Section: Figmentioning

confidence: 99%

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Accumulation-Associated Protein Enhances Staphylococcus epidermidis Biofilm Formation under Dynamic Conditions and Is Required for Infection in a Rat Catheter Model

et al. 2015

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Biofilm formation is the primary virulence factor of Staphylococcus epidermidis. S. epidermidis biofilms preferentially form on abiotic surfaces and may contain multiple matrix components, including proteins such as accumulation-associated protein (Aap). Following proteolytic cleavage of the A domain, which has been shown to enhance binding to host cells, B domain homotypic interactions support cell accumulation and biofilm formation. To further define the contribution of Aap to biofilm formation and infection, we constructed an aap allelic replacement mutant and an icaADBC aap double mutant. When subjected to fluid shear, strains deficient in Aap production produced significantly less biofilm than Aap-positive strains. To examine the in vivo relevance of our findings, we modified our previously described rat jugular catheter model and validated the importance of immunosuppression and the presence of a foreign body to the establishment of infection. The use of our allelic replacement mutants in the model revealed a significant decrease in bacterial recovery from the catheter and the blood in the absence of Aap, regardless of the production of polysaccharide intercellular adhesin (PIA), a well-characterized, robust matrix molecule. Complementation of the aap mutant with full-length Aap (containing the A domain), but not the B domain alone, increased initial attachment to microtiter plates, as did in trans expression of the A domain in adhesion-deficient Staphylococcus carnosus. These results demonstrate Aap contributes to S. epidermidis infection, which may in part be due to A domain-mediated attachment to abiotic surfaces.

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Section: Figsupporting

confidence: 64%

Section: Figmentioning

confidence: 99%

Accumulation-Associated Protein Enhances Staphylococcus epidermidis Biofilm Formation under Dynamic Conditions and Is Required for Infection in a Rat Catheter Model

et al. 2015

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“…Delivery of the challenge inoculum directly into the catheter lumen (37,38) is not suitable for vaccine or passive antibody studies because the bacteria are protected from host humoral and cell-mediated effectors. Likewise, intravascular injection of bacteria to achieve hematogenous colonization of the external catheter surface is highly problematic because megadoses (Ͼ10 9 cells) of bacteria are required (39) and it is impossible to distinguish whether the intervention is targeting the planktonic form or the biofilm form. Further, given that the ideal strategy is to inhibit biofilm formation at its earliest stages, it is not practical to surgically implant catheters with preformed biofilms to circumvent the catheter colonization issue.…”

Section: Discussionmentioning

confidence: 99%

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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“…For UTI, in vitro and in vivo studies demonstrated that immunization with FimH or components of the P pilus from UPEC reduced in vivo colonization of the bladder mucosa (319,320). For CVC-related infections, a rat model enabled assessment of immunization of rats prior to catheter insertion, leading to a protective effect in bacterial colonization of the device by S. aureus or S. epidermidis (321). 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).…”

Section: Targeting Biofilm Recalcitrance: Progress and Perspectivesmentioning

confidence: 99%

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

Lebeaux

Ghigo

Beloin

2014

Microbiol Mol Biol Rev

1,051

862

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International audienceSurface-associated microbial communities, called biofilms, are present in all environments. Although biofilms play an important positive role in a variety of ecosystems, they also have many negative effects, including biofilm-related infections in medical settings. The ability of pathogenic biofilms to survive in the presence of high concentrations of antibiotics is called "recalcitrance" and is a characteristic property of the biofilm lifestyle, leading to treatment failure and infection recurrence. This review presents our current understanding of the molecular mechanisms of biofilm recalcitrance toward antibiotics and describes how recent progress has improved our capacity to design original and efficient strategies to prevent or eradicate biofilm-related infections

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Development of a rat central venous catheter model for evaluation of vaccines to preventStaphylococcus epidermidisandStaphylococcus aureusearly biofilms

Cited by 16 publications

References 39 publications

Accumulation-Associated Protein Enhances Staphylococcus epidermidis Biofilm Formation under Dynamic Conditions and Is Required for Infection in a Rat Catheter Model

Accumulation-Associated Protein Enhances Staphylococcus epidermidis Biofilm Formation under Dynamic Conditions and Is Required for Infection in a Rat Catheter Model

Antibodies to PhnD Inhibit Staphylococcal Biofilms

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

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