In vivo production of exotoxin A and its role in endogenous Pseudomonas aeruginosa septicemia in mice.
We have examined the production of Pseudomonas aeruginosa exotoxin A (ETA) and its role in endogenous bacteremia in mice. Mice given P. aeruginosa D4 orally died of bacteremia between days 10 and 13 following cyclophosphamide-induced leukocytopenia. In this model, serum endotoxin was detected beginning on day 7 by the Limulus assay and P. aeruginosa was cultured from blood beginning on day 9. ETA and tumor necrosis factor alpha (TNF) were also detected in serum by enzyme-linked immunosorbent assay beginning on day 9. Purified ETA did not stimulate the production of TNF in normal mice primed with a synthetic derivative of muramyl dipeptide in the absence of endotoxin. However, ETA enhanced and primed endotoxin-induced TNF production in mice. The mortality rate of mice given ETA mutant PAO-PRI (5.0%) was significantly lower than that of mice given the parent strain (78.8%). These data indicate that ETA may be an important factor in the occurrence of P. aeruginosa bacteremia and/or the death of mice. Also, ETA may be responsible for enhancing the production of a lethal dose of TNF in the presence of endotoxin in P. aeruginosa bacteremia.
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
Y
Y
Hirakata
N
N
Furuya
K
K
Tateda
M
M
Kaku
K
K
Yamaguchi
D036002:ADP Ribose Transferases; D000818:Animals; D016470:Bacteremia / Q000209:etiology* / Q000378:metabolism; D001427:Bacterial Toxins / Q000096:biosynthesis*; D005098:Exotoxins / Q000096:biosynthesis* / Q000502:physiology; D008297:Male; D051379:Mice; D011552:Pseudomonas Infections / Q000209:etiology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A