Inhibition of filamentation can be used to treat disseminated candidiasis.

Abstract:

:Candida albicans remains the leading causative agent of invasive fungal infection. Although the importance of filamentation in C. albicans pathogenesis has been extensively investigated, in vivo studies to date have been unable to dissect the role of this developmental process in the establishment of infection versus the development of active disease as characterized by damage to the host leading to mortality. To address this issue, we genetically engineered a C. albicans tet-NRG1 strain in which filamentation and virulence can be modulated both in vitro and in vivo simply by the presence or absence of doxycycline (DOX): this strain enabled us, in a prior study, to demonstrate that yeast-form cells were able to infect the deep organs but caused no disease unless filamentation (induced by the addition of DOX) was allowed to occur. In the present study, we examined whether inhibiting filamentation (by withdrawing the DOX) at 24 or 48 h postinfection could serve as an effective therapeutic intervention against candidiasis. The results obtained indicate that DOX removal led to an alteration in the morphology of the infecting fungal cells and a dramatic increase in survival, but as with conventional antifungal drug therapy regimens, mortality rates increased markedly the longer this intervention was delayed. These observations reinforce the importance of invasive filamentous growth in causing the damage to the host and the lethality associated with active disease and suggest this process could be fruitfully targeted for the development of new antifungal agents.

authors

Saville SP,Lazzell AL,Bryant AP,Fretzen A,Monreal A,Solberg EO,Monteagudo C,Lopez-Ribot JL,Milne GT

doi

10.1128/AAC.00628-06

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

3312-6

issue

10

eissn

0066-4804

issn

1098-6596

pii

50/10/3312

journal_volume

50

pub_type

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