New Perspectives on Prevention and Management of Pseudomonas Aeruginosa Infections

Rumbaugh, Kendra P.; Sawa, Teiji; Wiener-Kronish, Jeanine P.

doi:10.1007/978-1-4615-0433-7_12

Cited by 1 publication

(1 citation statement)

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“…Several of these factors were used as candidates for immunotherapy or immunoprophylaxis to combat P. aeruginosa infections. Antibodies against antigenic molecules such as multivalent lipopolysaccharides (LPS), exotoxin A, flagella, mucoid exopolysacharide, and outer membrane protein had shown potential benefits against P. aeruginosa both in vitro and in vivo during initial investigations (14, 24). However, these vaccines never gained clinical acceptance due to a wide array of problems (24).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV – Implications for anti-PcrV immunotherapy

Lynch

Flanagan

Sawa

et al. 2010

Microbial Pathogenesis

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The type III secretion system of P. aeruginosa, responsible for acute infection, is composed of over twenty proteins that facilitate cytotoxin injection directly into host cells. Integral to this process is production and secretion of PcrV. Administration of a recently developed, anti-PcrV immunoglobulin, either as a therapeutic or prophylactic has previously demonstrated efficacy against laboratory strains of P. aeruginosa in a murine model. To determine if this therapy is universally applicable to a variety of P. aeruginosa clinical isolates, genetic heterogeneity of pcrV was analyzed among strains collected from three geographically distinct regions; United States, France and Japan. Sequence analysis of PcrV demonstrated limited variation among the clinical isolates examined. Strains were grouped according to the presence of non-synonymous single nucleotide polymorphisms. Representative isolates from each mutant group were examined for the ability of anti-PcrV to bind the protein secreted by these strains. The protective effect of anti-PcrV IgG against each strain was determined using an epithelial cell line cytotoxicity assay. The majority of strains tested demonstrated reduced cytotoxicity in the presence of anti-PcrV IgG. This study provides insights into the natural sequence variability of PcrV and an initial indication of the amino acid residues that appear to be conserved across strains. It also demonstrates the protective effect of anti-PcrV immunotherapy against a multitude of P. aeruginosa strains from diverse global regions with a variety of mutations in PcrV.

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Section: Introductionmentioning

confidence: 99%