Role of exotoxin A in inducing severe Pseudomonas aeruginosa infections in mice.
The effects of exotoxin A (EXA) from Pseudomonas aeruginosa on polymorphonuclear leucocytes (PMNLs) were studied in a mouse model and in vitro. P. aeruginosa PA103, which produced EXA, was 20 times more virulent for normal mice than was its EXA-deficient mutant, PA103-29. EXA was detected in the plasma of mice infected with P. aeruginosa PA103, and its presence correlated with increasing numbers of bacteria in the blood and internal organs. A monoclonal antibody (MAb) against EXA prevented the death of the mice if it was given simultaneously with, or 2 h before, infection with strain PA103. The number of PMNLs in murine blood decreased by 50% within 30 min of intravenous injection of EXA, but this decrease was prevented by simultaneous or prior injection of MAb to the toxin. EXA inhibited in-vitro phagocytosis and killing of P. aeruginosa by human and murine PMNLs and decreased the number of the PMNLs by between 60 and 68%. Collectively, these results not only confirm that EXA is toxic in vivo, but also suggest that this toxin accelerates the growth of virulent P. aeruginosa in mice.
Miyazaki
S
S
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
Matsumoto
T
T
Tateda
K
K
Ohno
A
A
Yamaguchi
K
K
D036002:ADP Ribose Transferases; D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000276:immunology / Q000633:toxicity; D004195:Disease Models, Animal; D005098:Exotoxins / Q000096:biosynthesis* / Q000276:immunology / Q000633:toxicity; D007928:Lethal Dose 50; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009503:Neutropenia / Q000276:immunology / Q000382:microbiology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors; D014781:Viscera / Q000382:microbiology; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D008070:Lipopolysaccharides; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A