Generation and characterization of a protective monoclonal antibody to Pseudomonas aeruginosa PcrV.
Pseudomonas aeruginosa is a gram-negative pathogen causing life-threatening infections. Lung injury and the development of sepsis depend largely on the expression of type III secretion system (TTSS) virulence. TTSS functions as a molecular syringe to deliver toxins directly to the cytosol of cells, inhibit innate immune mechanisms, and prevent bacterial clearance. Polyclonal antibodies that bind to PcrV of P. aeruginosa inhibit the delivery of type III toxins and enhance the clearance of bacteria during acute lung infections. PcrV is a homologue of LcrV, a protective antigen in the Yersinia TTSS and an integral component of TTSS. In this study, a murine monoclonal antibody (MAb) to PcrV was generated: MAb 166, which is protective against P. aeruginosa when coinstilled with the bacterial inoculum or intraperitoneally transferred to mice. Fab fragments from MAb 166 prevent sepsis and death. The epitope bound by MAb 166 was mapped to the carboxyl-terminus of PcrV.
Frank
Dara W
DW
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Vallis
Amy
A
Wiener-Kronish
Jeanine P
JP
Roy-Burman
Arup
A
Spack
Edward G
EG
Mullaney
Brian P
BP
Megdoud
Mehdi
M
Marks
James D
JD
Fritz
Robert
R
Sawa
Teiji
T
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D004195:Disease Models, Animal; D018604:Epitope Mapping; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052899:Pore Forming Cytotoxic Proteins; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007140:Immunoglobulin Fab Fragments; D052899:Pore Forming Cytotoxic Proteins; C118546:antigen V, Pseudomonas