Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection

Abstract

The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b ofPseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infection in burned mice, while it was much less active against intraperitoneal infection in normal mice. In a burn infection model, IN-2A8 inhibited the increase of bacteria in skin lesions weakly and that in blood significantly, suggesting that it strongly suppressed bacterial spread to blood. The activity of IN-2A8 in combination with 10 antipseudomonal antibiotics against intraperitoneal infection was examined. Clear additive effect was observed with a combination of either carbapenem or aminoglycoside antibiotics in terms of mouse survival. The administration of an antibiotic, imipenem-cilastatin, simultaneously with or before that of IN-2A8 gave a combined effect, but the reverse order did not. The combination of IN-2A8 with imipenem-cilastatin decreased numbers of viable bacteria in the peritoneal cavity and blood and kept them low for a longer time than did either treatment alone. These results suggest that an antiflageUar monoclonal antibody would be effective against systemic infection in combination with some kinds of antibiotics.

Cooperation between LepA and PlcH Contributes to theIn VivoVirulence and Growth ofPseudomonas aeruginosain Mice

“…Challenge of leukopenic mice by i.p. injection with P. aeruginosa was reported to cause sepsis by acute systemic infection, leading to the death of mice within 1 to 3 days after infection (32,56). In our in vivo model, leukopenic mice infected i.p.…”

“…This model has been developed to study the pathogenesis of P. aeruginosa infection under immunosuppressed conditions and to evaluate therapeutic agents (10,56). Challenge of leukopenic mice by i.p.…”

EprS, an autotransporter serine protease, plays an important role in various pathogenic phenotypes of Pseudomonas aeruginosa

“…Challenge of leucopenic mice by i.p. injection with P. aeruginosa was reported to cause sepsis by acute systemic infection, leading to the death of mice within 1 to 3 days after infection (Miyazaki et al, 1995;Uezumi et al, 1992). We previously demonstrated that EprS activates NF-kB-driven promoter through PAR-1, -2, or -4 and induces IL-8 production through PAR-2 in a human bronchiole epithelial cell line (Kida et al, 2013).…”

“…6). This model has been developed to study the pathogenesis of P. aeruginosa infection under immunosuppressed conditions and to evaluate the therapeutic agents (Cryz et al, 1983;Uezumi et al, 1992). Challenge of leucopenic mice by i.p.…”

Recent developments for Pseudomonas vaccines

“…208 Similarly, several antibodies targeting other virulence-associated antigens of P. aeruginosa such as flagella, 75,78,79,[209][210][211][212] …”