Pathogenesis of pulmonary Cryptococcus gattii infection: a rat model.

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 10(4) to 10(7) 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 10(7) 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 10(6) CFU i.t. did not produce lesions, while 10(7) 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.

journal_name

Mycopathologia

journal_title

Mycopathologia

authors

Krockenberger MB,Malik R,Ngamskulrungroj P,Trilles L,Escandon P,Dowd S,Allen C,Himmelreich U,Canfield PJ,Sorrell TC,Meyer W

doi

10.1007/s11046-010-9328-z

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

315-30

issue

5

eissn

0301-486X

issn

1573-0832

journal_volume

170

pub_type

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