Bacillus thuringiensis pulmonary infection: critical role for bacterial membrane-damaging toxins and host neutrophils.
The occurrence of Bacillus thuringiensis bacteremia in a neutropenic patient suffering from severe pulmonary disease addressed the question of whether the aggressive behavior of B. thuringiensis depended on the host status and/or on the membrane-damaging toxins the isolate produced. After intratracheal injection, BALB/c mice developed pneumonia followed by fatal dissemination into deep organs, with mice rendered neutropenic by cyclophosphamide injection being extremely more susceptible to infection than normal animals. In animals infected with isogenic strains of B. thuringiensis progressively more defective in membrane-damaging toxins (407 Cry->IP2>MP02), an increase in the 50% lethal dose was registered (3.9x10(5), 1.1x10(6), 1.2x10(7)CFU). Consistently, after non-lethal dose application, only 407 Cry- replicated intrapulmonary, reaching a bacterial burden 4.7-fold and 40.9-fold higher than IP2 (P=0.018) and MP02 (P=0.008) at 48h post-inoculation. Notably, the time-course of infection was similar in animals infected with viable bacilli or spores, with neutropenic mice always being more susceptible to infection. The overall results indicate that B. thuringiensis may be responsible for opportunistic infections and strongly suggest that membrane-damaging toxins contribute to intrapulmonary bacterial persistence favoring dissemination.
Ghelardi
Emilia
E
Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università di Pisa, Via San Zeno 37, 56127 Pisa, Italy.
Celandroni
Francesco
F
Salvetti
Sara
S
Fiscarelli
Ersilia
E
Senesi
Sonia
S
D000818:Animals; D016863:Bacillaceae Infections / Q000503:physiopathology; D001413:Bacillus thuringiensis / Q000737:chemistry*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D006460:Hemolysin Proteins / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000382:microbiology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C