title: Role of filamentation in Galleria mellonella killing by Candida albicans.
abstract: Candida albicans is an important cause of morbidity in hospitalized and immunosuppressed patients. Virulence factors of C. albicans include: filamentation, proteinases, adherence proteins and biofilm formation. The objective of this work was to use Galleria mellonella as a model to study the roles of C. albicans filamentation in virulence. We focused our study to five genes BCR1, FLO8, KEM1, SUV3 and TEC1 that have been shown to play a role in filamentation. Filaments are necessary for biofilm formation and evading interaction with macrophages in mammalian infections. Among the five mutant strain tested, we found that only the flo8/flo8 mutant strain did not form filaments within G. mellonella. This strain also exhibited reduced virulence in the larvae. Another strain that exhibited reduced pathogenicity in the G. mellonella model was tec1/tec1 but by contrast, the tec1/tec1 strain retained the ability to form filaments. Overexpression of TEC1 in the flo8/flo8 mutant restored filamentation but did not restore virulence in the larvae as well as in a mouse model of C. albicans infection. The filamentation phenotype did not affect the ability of hemocytes, the immune cells of G. mellonella, to associate with the various mutant strains of C. albicans. The capacities of the tec1/tec1 mutant and the flo8/flo8 TDH3-TEC1 strains to form filaments with impaired virulence suggest that filamentation alone is not sufficient to kill G. mellonella and suggest other virulence factors may be associated with genes that regulate filamentation.
authors.affiliation: Division of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA. hfuchs@partners.org
authors.forename: Beth Burgwyn
authors.initials: BB
authors.lastname: Fuchs
authors.forename: Josh
authors.initials: J
authors.lastname: Eby
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Nobile
authors.forename: Joseph B
authors.initials: JB
authors.lastname: El Khoury
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Mitchell
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D025301:Hyphae / Q000235:genetics / Q000472:pathogenicity; D053208:Kaplan-Meier Estimate; D051379:Mice; D009036:Moths / Q000382:microbiology*