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Pathogenesis of Pulmonary Cryptococcus gattii Infection: A Rat Model |
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| Authors: | Mark B. Krockenberger Richard Malik Popchai Ngamskulrungroj Luciana Trilles Patricia Escandon Susan Dowd Chris Allen Uwe Himmelreich Paul J. Canfield Tania C. Sorrell Wieland Meyer |
| Affiliation: | 1. Faculty of Veterinary Science, Building B14, University of Sydney, Sydney, NSW, 2006, Australia 2. Centre for Veterinary Education, Conference Centre, Building B22, The University of Sydney, Sydney, NSW, 2006, Australia 3. Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute, Western Clinical School, University of Sydney, Westmead, NSW, 2145, Australia 4. Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand 5. Mycology Laboratory, Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation. Av. Brazil, 4365, 21040-900, Rio de Janeiro, Brazil 6. Grupo de Microbiología, Instituto Nacional de Salud, Bogotá, Colombia 9. Royal Children’s Hospital, Herston Road, Herston, QLD, 4006, Australia 7. Max Planck Institute for Neurological Research, K?ln, 50931, Germany 8. Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute, Western Clinical School, University of Sydney, Westmead, NSW, 2145, Australia |
| Abstract: | A model of pulmonary cryptococcosis in immunocompetent rats was developed to better understand the virulence of Cryptococcus gattii. Six isolates were studied, representing four molecular genotypes (VGI-MATα, VGIIa-MATα, VGIIa-MAT a, VGIIb-MATα), obtained from Australia, Vancouver (Canada) and Colombia. These originated from human patients, a cat and the environment and were administered intratracheally (i.t.) or transthoracically into Fischer 344 or Wistar-Furth rats in doses varying from 104 to 107 colony-forming units (CFU) in 0.1 ml of saline. With the exception of animals given the VGIIa-MAT a isolate, rats consistently became ill or died of progressive cryptococcal pneumonia following i.t. doses exceeding 107 CFU. Affected lungs increased in weight up to tenfold and contained numerous circumscribed, gelatinous lesions. These became larger and more extensive, progressing from limited hilar and/or tracheal lesions, to virtually confluent gelatinous masses. Disease was localized to the lungs for at least 3–4 weeks, with dissemination to the brain occurring in some animals after day 29. The dose–response relationship was steep for two VGI isolates studied (human WM179, environmental WM276); doses up to 106 CFU i.t. did not produce lesions, while 107 or more yeast cells produced progressive pneumonia. Intratracheal inoculation of rats with C. gattii provides an excellent model of human pulmonary cryptococcosis in healthy hosts, mimicking natural infections. Disease produced by C. gattii in rats is distinct from that caused by C. neoformans in that infections are progressive and ultimately fatal. |
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