Broadly Protective Vaccine for
            <i>Staphylococcus aureus</i>
            Based on an in Vivo-Expressed Antigen

McKenney, David; Pouliot, Kimberly; Wang, Ying; Murthy, Vivek; Ulrich, Martina; Döring, Gerd; Lee, Jean C.; Goldmann, Donald A.; Pier, Gerald B.

doi:10.1126/science.284.5419.1523

Cited by 334 publications

(305 citation statements)

References 40 publications

Supporting

Mentioning

289

Contrasting

Unclassified

Order By: Relevance

“…CFT1-LCFSN cells were incubated with P. aeruginosa PAO1-V for 4 h. Unbound bacteria were washed away with PBS. Staining for LPS was carried out as described by using normal or immune serum and Protein A gold particles for visualization by electron microscopy (14). Images were taken at a magnification of ϫ25,000.…”

Section: Nf-b Activationmentioning

confidence: 99%

CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-κB translocation

Schroeder

Lee

Yacono

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

125

View full text Add to dashboard Cite

Immune cells are activated during cellular responses to antigen by two described mechanisms: (i) direct uptake of antigen and (ii) extraction and internalization of membrane components from antigen-presenting cells. Although endocytosis of microbial antigens by pattern recognition molecules (PRM) also activates innate immunity, it is not known whether this involves extraction and internalization of microbial surface components. Epithelial cells on mucosal surfaces use a variety of receptors that are distinct from the classical endocytic PRM to bind and internalize intact microorganisms. Nonclassical receptor molecules theoretically could act as a type of endocytic PRM if these molecules could recognize, bind, extract, and internalize a pathogen-associated molecule and initiate cell signaling. We report here that the interaction between the cystic fibrosis transmembrane conductance regulator (CFTR) and the outer core oligosaccharide of the lipopolysaccharide (LPS) in the outer membrane of Pseudomonas aeruginosa satisfies all of these conditions. P. aeruginosa LPS was specifically recognized and bound by CFTR, extracted from the organism's surface, and endocytosed by epithelial cells, leading to a rapid (5-to 15-min) and dynamic translocation of nuclear transcription factor NF-B. Inhibition of epithelial cell internalization of P. aeruginosa LPS prevented NF-B activation. Cellular activation depended on expression of wild-type CFTR, because both cultured ⌬F508 CFTR human airway epithelial cells and lung epithelial cells of transgenic-CF mice failed to endocytose LPS and translocate NF-B. CFTR serves as a critical endocytic PRM in the lung epithelium, coordinating the effective innate immune response to P. aeruginosa infection.

show abstract

Section: Nf-b Activationmentioning

confidence: 99%

CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-κB translocation

Schroeder

Lee

Yacono

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

125

View full text Add to dashboard Cite

show abstract

“…have potential as a vaccine candidate against staphylococcal disease (Joyce et al, 2003;Maira-Litran et al, 2002;McKenney et al, 1999McKenney et al, , 2000Tojo et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Genetic and phenotypic analysis of biofilm phenotypic variation in multiple Staphylococcus epidermidis isolates

Handke

Conlon

Slater

et al. 2004

Journal of Medical Microbiology

View full text Add to dashboard Cite

Production of biofilm in Staphylococcus epidermidis is mediated through enzymes produced by the four-gene operon ica and is subject to phenotypic variation. The purpose of these experiments was to investigate the regulation of ica and icaR transcription in phenotypic variants produced by multiple unrelated isolates of S. epidermidis. Ten isolates were chosen for the study, four of which contained IS256. IS256 mediates a reversible inactivation of ica in approximately 30 % of phenotypic variants. All ten strains produced at least two types of phenotypic variant (intermediate and smooth) in which biofilm formation was significantly impaired. Reversion studies indicated that all phenotypic variants were stable after overnight growth, but began to revert to other phenotypic forms after 5 days of incubation at 37 8C. ica transcriptional analysis was performed on phenotypic variants from three IS256-negative isolates; 1457, SE5 and 14765. This analysis demonstrated that ica transcription was significantly reduced in the majority of phenotypic variants, although two variants from SE5 and 1457 produced wild-type quantities of ica transcript. Analysis of seven additional phenotypic variants from SE5 revealed that ica expression was only reduced in three. Expression of icaR transcript was unaffected in all smooth phenotypic variants. Mutations within ica were identified in two SE5 variants with wild-type levels of ica transcription. It is concluded that mutation and transcriptional regulation of ica are the primary mechanisms that govern phenotypic variation of biofilm formation within IS256-negative S. epidermidis.

show abstract

“…A wide variety of medically important biofilm-forming bacteria produce partially de-N-acetylated poly-␤-1,6-N-acetyl-D-glucosamine (dPNAG) 5 exopolysaccharides, also referred to as polysaccharide intercellular adhesin. dPNAG was first described in Staphylococcus epidermidis (8) but has now been determined to be a component of the biofilm matrices of Staphylococcus aureus (9), Escherichia coli (10), Acinetobacter baumannii (11), Bordetella bronchiseptica (12), Bordetella pertussis (13), Actinobacillus pleuropneumoniae (14), Yersinia pestis (15), and Burkholderia species (16).…”

mentioning

confidence: 99%

The Structure- and Metal-dependent Activity of Escherichia coli PgaB Provides Insight into the Partial De-N-acetylation of Poly-β-1,6-N-acetyl-d-glucosamine

Little

Poloczek

Whitney

et al. 2012

Journal of Biological Chemistry

114

View full text Add to dashboard Cite

Background: Polysaccharide intercellular adhesin-dependent biofilm formation in E. coli requires the de-N-acetylation of poly-␤-1,6-N-acetyl-D-glucosamine by PgaB. Results: Nickel-and iron-bound structures of PgaB have been determined, and the metal-dependent de-N-acetylase activity of the enzyme has been characterized. Conclusion: PgaB has low catalytic efficiency and shows preference for Co 2ϩ , Ni 2ϩ , and Fe 2ϩ ions. Significance: The structure of PgaB will guide inhibitor design to combat biofilm formation.

show abstract

Broadly Protective Vaccine for Staphylococcus aureus Based on an in Vivo-Expressed Antigen

Cited by 334 publications

References 40 publications

CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-κB translocation

CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-κB translocation

Genetic and phenotypic analysis of biofilm phenotypic variation in multiple Staphylococcus epidermidis isolates

The Structure- and Metal-dependent Activity of Escherichia coli PgaB Provides Insight into the Partial De-N-acetylation of Poly-β-1,6-N-acetyl-d-glucosamine

Contact Info

Product

Resources

About