Identification of broadly protective human antibodies to<i>Pseudomonas aeruginosa</i>exopolysaccharide Psl by phenotypic screening

DiGiandomenico, Antonio; Warrener, Paul; Hamilton, Melissa; Guillard, Sandrine; Ravn, Peter; Minter, Ralph; Câmara, Maria Clara Coelho; Venkatraman, Vignesh; MacGill, Randall S.; Lin, Jianqiang; Wang, Qun; Keller, Ashley; Bonnell, Jessica; Tomich, Mladen; Jermutus, Lutz; McCarthy, Michael; Melnick, David; Suzich, JoAnn; Stover, C. Kendall

doi:10.1084/jem.20120033

Cited by 147 publications

(186 citation statements)

References 56 publications

(105 reference statements)

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“…It stands to reason that Psl also plays an important role during this process based on its adherence and aggregation functions. Moreover, recent studies indicate potential roles for Psl in promoting immune evasion (24), and passive immunization studies show that antibodies generated against Psl can provide protection against P. aeruginosa infection (25).…”

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confidence: 99%

AmrZ Modulates Pseudomonas aeruginosa Biofilm Architecture by Directly Repressing Transcription of thepslOperon

et al. 2013

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e Pseudomonas aeruginosa strains recovered from chronic pulmonary infections in cystic fibrosis patients are frequently mucoid. Such strains express elevated levels of alginate but reduced levels of the aggregative polysaccharide Psl; however, the mechanistic basis for this regulation is not completely understood. Elevated pslA expression was observed in an amrZ null mutant and in strains expressing a DNA-binding-deficient AmrZ. AmrZ is a transcription factor that positively regulates twitching motility and alginate synthesis, two phenotypes involved in P. aeruginosa biofilm development. AmrZ bound directly to the pslA promoter in vitro, and molecular analyses indicate that AmrZ represses psl expression by binding to a site overlapping the promoter. Altered expression of amrZ in nonmucoid strains impacted biofilm structure and architecture, as structured microcolonies were observed with low AmrZ production and flat biofilms with amrZ overexpression. These biofilm phenotypes correlated with Psl levels, since we observed elevated Psl production in amrZ mutants and lower Psl production in amrZ-overexpressing strains. These observations support the hypothesis that AmrZ is a multifunctional regulator mediating transition of P. aeruginosa biofilm infections from colonizing to chronic biofilms through repression of the psl operon while activating the algD operon.

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confidence: 99%

AmrZ Modulates Pseudomonas aeruginosa Biofilm Architecture by Directly Repressing Transcription of thepslOperon

et al. 2013

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“…Antibodies specific for surface antigens of P. aeruginosa are important for opsonin-mediated phagocytosis of this pathogen, a phenomenon associated with protective immunity. 19 Mice were immunized by intranasal (i.n.) administration with individual recombinant F. tularensis LVS strains (LVS / pBR, LVS / pOPRF, or LVS / pGFLI), LVS alone, or phosphate buffered saline (PBS).…”

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confidence: 99%

Genetic engineering ofFrancisella tularensisLVS for use as a novel live vaccine platform againstPseudomonas aeruginosainfections

Robinson

Kobe

Schmitt³

et al. 2015

Bioengineered

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“…By construction and phenotypic screening of human scFv phage display libraries from peripheral blood B cells of healthy individuals and patients recovered from recent P. aeruginosa infections, mAbs against one epitope of Psl, the exopolysaccharide important for P. aeruginosa atachment to host cell and bioilm maintenance, was identiied to show potent protection in several animal P. aeruginosa infection models [119]. Also, this inding suggests that PsI can be used as a vaccine target.…”

Section: Antibody and Vaccine Development Against Psimentioning

confidence: 99%

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

Zhang¹,

Su²,

Wu³

2017

Physiology and Pathology of Immunology

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Multidrug-resistant bacteria (MDR) are increasing rapidly and posing a global threat to mankind. Alternative strategies other than antibiotics have to be explored urgently. In this chapter, we review the current status of nonantibiotics strategies including antibodybased therapy and vaccine development for targeting Gram-positive strains (methicillinresistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium) and MDR Gram-negative strains (Acinetobacter baumannii and Pseudomonas aeruginosa). Biologicsbased clinical progress against these bacterial infections is updated.

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Identification of broadly protective human antibodies toPseudomonas aeruginosaexopolysaccharide Psl by phenotypic screening

Abstract: A human antibody facilitates opsonophagocytic killing, inhibits attachment of Pseudomonas aeruginosa, and exerts protective effects in several animal models of P. aeruginosa infection.

Cited by 147 publications

References 56 publications

AmrZ Modulates Pseudomonas aeruginosa Biofilm Architecture by Directly Repressing Transcription of thepslOperon

AmrZ Modulates Pseudomonas aeruginosa Biofilm Architecture by Directly Repressing Transcription of thepslOperon

Genetic engineering ofFrancisella tularensisLVS for use as a novel live vaccine platform againstPseudomonas aeruginosainfections

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

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