154 A MANUAL OF THE ASPERGILLI 



Pathogenesis 



There is an extensive pathological literature which covers the occurrence 

 of A. fumigatus in lesions of birds and mammals, including man, together 

 with biochemical and animal experimentation. Such experiments have 

 repeatedly proved that the organism is pathogenic to fowls confined in con- 

 gested quarters in which moldy grain, straw, and other plant remains are 

 abundant. Direct inoculation to the cornea in laboratory animals causes 

 lesions characteristic for the species. 



Infection of human beings occasionally appears, and observations seem 

 to indicate that the patients generally have been exposed to air carrying 

 large numbers of spores. Allergists have reported asthmatic conditions 

 arising from sensitization to this species, and Bern ton (1930) reports having 

 successfully treated a patient by means of an extract prepared from the 

 spores and mycelium of A. fumigatus. The occurrence of A. fischeri in 

 cases grouped with A. fumigatus is clear indication that the pathogenic 

 principle, whatever it is, is generally present in the group although it may 

 vary in its intensity among different strains as indicated by workers such 

 as Costantin and Lucet (1905). 



Among organisms known to be, or believed to have been, pathogenic 

 strains of A. fumigatus, the following named forms may be cited: A. 

 gratioti, A. malignus, A. fumigatoides, A. virido-griseus, A. bronchialis, A. 

 glaucoides, A. nigrescens, A. pulmonum hominis, A. ramosus, and A. avia- 

 rius (see p. 151). For a more complete discussion of this group in relation 

 to disease in birds and mammals, the reader is referred to Thorn and 

 Church's The Aspergilli (1926) and Dodge's Medical Mycology (1935). 



Antibiosis 



Anslow and Raistrick (1938a) reported the production by Aspergillus 

 fumigatus of a substance to which they applied the name, fumigatin, and in 

 the same year (1938b) reported the species to produce a second metabolic 

 product termed spinulosin, which they had previously isolated from Peni- 

 cillium spinulosum. In 1942 fumigatin was further discussed by Oxford 

 and Raistrick as a powerful agent against such bacteria as Bacillus anthra- 

 cis, Escherichia coli, Salmonella typhi-murinum, Staphylococcus albus, S. 

 aureus, Streptococcus viridans, and Vibrio cholorae. Also in 1942 Waksman, 

 Horning, and Spencer reported an antibiotic substance, termed fumigacin, 

 to be produced by A. fumigatus, and presented methods of differentiating 

 this from fumigatin as studied by Raistrick and associates. Fumigacin was 

 found to be both bactericidal and bacteriostatic in its action and to be 

 effective in fairly high dilutions in inhibiting the growth of gram -positive 

 cocci and bacilli ; it was much less effective against the gram-negative mem- 

 bers of the coli-aerogenes group. Both fumigatin and fumigacin have been 

 found toxic to experimental animals. 



