Pathogenesis of Pulmonary Cryptococcus gattii Infection: A Rat Model

• Published in: Mycopathologia (1975) Vol. 170; no. 5; pp. 315 - 330
• Main Authors: Krockenberger, Mark B, Malik, Richard, Ngamskulrungroj, Popchai, Trilles, Luciana, Escandon, Patricia, Dowd, Susan, Allen, Chris, Himmelreich, Uwe, Canfield, Paul J, Sorrell, Tania C, Meyer, Wieland
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : Springer Netherlands 01-11-2010; Springer Netherlands; Springer; Springer Nature B.V
• Subjects: Animals; Australia; Bacterial pneumonia; Biomedical and Life Sciences; Brain - microbiology; Brain - pathology; Canada; Cat Diseases - microbiology; Cats; Colombia; Cryptococcosis; Cryptococcosis - microbiology; Cryptococcosis - mortality; Cryptococcosis - pathology; Cryptococcus; Cryptococcus gattii - classification; Cryptococcus gattii - isolation & purification; Cryptococcus gattii - pathogenicity; Disease Models, Animal; Environmental Microbiology; Eukaryotic Microbiology; Female; Gattii; Health aspects; Humans; Infections; Infectious diseases; Life Sciences; Lung; Lung - microbiology; Lung - pathology; Lung Diseases, Fungal - microbiology; Lung Diseases, Fungal - mortality; Lung Diseases, Fungal - pathology; Lungs; Male; Medical Microbiology; Meningitis; Microbial Ecology; Microbiology; Mycoses; Pathogenesis; Plant Sciences; Pneumonia; Rats; Rats, Inbred F344; Rats, Inbred WF; Time Factors; Virulence; Australia; Canada; Colombia; Brazil; Western Australia Australia; Cryptococcus; Meningitis; Rat; Lung; Cryptococcosis
• ISSN: 0301-486X; 1573-0832
• DOI: 10.1007/s11046-010-9328-z

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.