Virulence Attenuation of Candida albicans Genetic Variants Isolated from a Patient with a Recurrent Bloodstream Infection

• Type: Article in International Scientific Journal
• Date: 2010

Authors

sampaio, p (Author) Other; santos, m (Author) Other; Alexandra Correia (Author) ICBAS; amaral, fe (Author) Other; chavez-galarza, j (Author) Other; costa-de-oliveira, s (Author) FMUP; castro, ag (Author) Other; pedrosa, j (Author) Other; pais, c (Author) Other

Journal

Title: PLoS ONE

Vol. 5

ISSN: 1932-6203

Publisher: Public Library of Science

Indexing

ISI Web of Knowledge - 18 Citations

Scopus - 19 Citations

Other information

Authenticus ID: P-003-7GY

DOI: 10.1371/journal.pone.0010155

Abstract (EN): The incidence of Candida albicans infections and the relapse episodes after antifungal treatment have increased in recent decades. Recurrences are mainly due to the persistence of the original infecting strain that may present genetic and genomic rearrangements during interaction with the host, reflecting strain adaptation. In this study, four isolates recovered from a patient during recurrent candidemia episodes were genotyped by microsatellite length polymorphism (MLP) and by multilocus sequence typing (MLST) and found to be genetic variants of the same strain. Using experimental mouse infections, a progressive reduction in the virulence of the four isolates was observed, with the first two isolates more virulent than the third and fourth. Additionally, in the mouse model, the first isolate resisted host control more efficiently, resulting in higher kidney fungal burdens and necrosis as compared to the third isolate. The resolution of inflammation was delayed in mice challenged with the first isolate and the message for IFN-gamma and TNF-alpha in the spleen was lower within the first few hours post-infection. Original and recurrent isolates also displayed different phenotypes regarding activity of secreted enzymes and response to stress agents. Overall, the comparative analysis indicated that the virulence decrease of these isolates was related to a lower ability to resist to the host anticandida effector mechanisms. We showed for the first time that C. albicans genetic variants of the same strain, sequentially isolated from an immunocompromised patient, underwent adaptations in the human host that resulted in virulence attenuation when tested in mice.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10