title: Virulence attenuation of Candida albicans genetic variants isolated from a patient with a recurrent bloodstream infection.
abstract: 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.
authors.affiliation: Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Braga, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Sampaio
authors.forename: Marlene
authors.initials: M
authors.lastname: Santos
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.forename: Fábio E
authors.initials: FE
authors.lastname: Amaral
authors.forename: Julio
authors.initials: J
authors.lastname: Chavéz-Galarza
authors.forename: Sofia
authors.initials: S
authors.lastname: Costa-de-Oliveira
authors.forename: António G
authors.initials: AG
authors.lastname: Castro
authors.forename: Jorge
authors.initials: J
authors.lastname: Pedrosa
authors.forename: Célia
authors.initials: C
authors.lastname: Pais
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology*; D016469:Fungemia / Q000382:microbiology*; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014774:Virulence / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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