Toxic Effect of Products of Oxidative Metabolism on the Yeast Form of Paracoccidioides Brasiliensis

• Published in: Journal of medical microbiology Vol. 18; no. 3; pp. 423 - 428
• Main Authors: McEwen, J. G, Sugar, A. M, Brummer, E, Restrepo, Angela, Stevens, D. A
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01-12-1984; Society for General Microbiology
• Subjects: Biological and medical sciences; Catalase - pharmacology; Fundamental and applied biological sciences. Psychology; Fungi - drug effects; Horseradish Peroxidase - pharmacology; Hydrogen Peroxide - pharmacology; Kinetics; Lethal Dose 50; Microbiology; Mycology; Paracoccidioides - drug effects; Paracoccidioides - growth & development; Pathogenicity, host-agent relations, miscellaneous strains, epidemiology; Peroxidases - pharmacology; Potassium Iodide - pharmacology; Fungi; Sensitivity resistance; Yeast form; Metabolite; Toxicity; Blastomyces brasiliensis; Oxidation; Metabolism; Pathogen; Defense; Thallophyta
• ISSN: 0022-2615; 1473-5644
• DOI: 10.1099/00222615-18-3-423

Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, and Institute for Medical Research, San Jose, CA 95128, Stanford University, Stanford, CA 94305
* Corporacion de Investigaciones Biologicas, Medellin, Colombia
Address for correspondence and offprint requests: Dr D. A. Stevens, Division of Infectious Diseases, Santa Clara Valley Medical Center, 751 S. Bascom Avenue, San Jose, CA95128. USA.
Received December 21, 1983
Accepted May 30, 1984
The effectiveness of toxic oxygen metabolites in killing the yeast form of Paracoccidioides brasiliensis (the form that occurs in host tissues) was studied with a fluorescence method in vitro . The two isolates studied were similar in susceptibility and H 2 O 2 alone was lethal with an LD50 of 15–25 mM. The addition of halide (5 x 10 -4 M) augmented the lethality of H 2 O 2 and in that setting H 2 O 2 was c. 90% lethal at 5 x 10 -5 M. Killing was most effective in the presence of peroxidase, when only 5 x 10 -6 M H 2 O 2 (a concentration attainable in vivo by phagocytes) was required for a 95% kill. Kinetic studies revealed that toxic concentrations of H 2 O 2 alone or of the H 2 O 2 -halide-peroxidase (PPH) system produced significant killing in 1 min; killing was maximal in 15 min. The PPH system was the more rapid in action. The dependence of the PPH killing system on H 2 O 2 was demonstrated by an absence of killing in the presence of catalase. The susceptibility of P. brasiliensis to H 2 O 2 and the PPH system appeared different in some respects from that noted for other dimorphic fungal pathogens. These studies suggest that toxic oxygen metabolites are important in host defence against P. brasiliensis .