Vulvovaginal candidiasis (VVC) affects nearly 3/4 of women during their lifetime, and its symptoms seriously reduce quality of life. Although Candida albicans is a common commensal, it is unknown if VVC results from a switch from a commensal to pathogenic state, if only some strains can cause VVC, and/or if there is displacement of commensal strains with more pathogenic strains. We studied a set of VVC and colonizing C. albicans strains to identify consistent in vitro phenotypes associated with one group or the other. We find that the strains do not differ in overall genetic profile or behavior in culture media (i.e., multilocus sequence type [MLST] profile, rate of growth, and filamen- tation), but they show strikingly different behaviors during their interactions with vaginal epithelial cells. Epithelial infections with VVC-derived strains yielded stronger fungal prolif- eration and shedding of fungi and epithelial cells. Transcriptome sequencing (RNA-seq) analysis of representative epithelial cell infections with selected pathogenic or commensal isolates identified several differentially activated epithelial signaling pathways, including the integrin, ferroptosis, and type I interferon pathways; the latter has been implicated in damage protection. Strikingly, inhibition of type I interferon signaling selectively increases fungal shedding of strains in the colonizing cohort, suggesting that increased shedding correlates with lower interferon pathway activation. These data suggest that VVC strains may intrinsically have enhanced pathogenic potential via differential elicitation of epithelial responses, including the type I interferon pathway. Therefore, it may eventually be possible to evaluate pathogenic potential in vitro to refine VVC diagnosis.

A New Phenotype in Candida-Epithelial Cell Interaction Distinguishes Colonization- versus Vulvovaginal Candidiasis- Associated Strains / Sala, Arianna; Ardizzoni, Andrea; Spaggiari, Luca; Vaidya, Nikhil; van der Schaaf, Jane; Rizzato, Cosmeri; Cermelli, Claudio; Mogavero, Selene; Krüger, Thomas; Himmel, Maximilian; Kniemeyer, Olaf; Brakhage, Axel A.; King, Benjamin L.; Lupetti, Antonella; Comar, Manola; de Seta, Francesco; Tavanti, Arianna; Blasi, Elisabetta; Wheeler, Robert T.; Pericolini, Eva. - In: MBIO. - ISSN 2161-2129. - 14:2(2023), pp. 1-18. [10.1128/mbio.00107-23]

A New Phenotype in Candida-Epithelial Cell Interaction Distinguishes Colonization- versus Vulvovaginal Candidiasis- Associated Strains

Andrea Ardizzoni;Luca Spaggiari;Claudio Cermelli;Elisabetta Blasi;Eva Pericolini
2023

Abstract

Vulvovaginal candidiasis (VVC) affects nearly 3/4 of women during their lifetime, and its symptoms seriously reduce quality of life. Although Candida albicans is a common commensal, it is unknown if VVC results from a switch from a commensal to pathogenic state, if only some strains can cause VVC, and/or if there is displacement of commensal strains with more pathogenic strains. We studied a set of VVC and colonizing C. albicans strains to identify consistent in vitro phenotypes associated with one group or the other. We find that the strains do not differ in overall genetic profile or behavior in culture media (i.e., multilocus sequence type [MLST] profile, rate of growth, and filamen- tation), but they show strikingly different behaviors during their interactions with vaginal epithelial cells. Epithelial infections with VVC-derived strains yielded stronger fungal prolif- eration and shedding of fungi and epithelial cells. Transcriptome sequencing (RNA-seq) analysis of representative epithelial cell infections with selected pathogenic or commensal isolates identified several differentially activated epithelial signaling pathways, including the integrin, ferroptosis, and type I interferon pathways; the latter has been implicated in damage protection. Strikingly, inhibition of type I interferon signaling selectively increases fungal shedding of strains in the colonizing cohort, suggesting that increased shedding correlates with lower interferon pathway activation. These data suggest that VVC strains may intrinsically have enhanced pathogenic potential via differential elicitation of epithelial responses, including the type I interferon pathway. Therefore, it may eventually be possible to evaluate pathogenic potential in vitro to refine VVC diagnosis.
2023
1-mar-2023
14
2
1
18
A New Phenotype in Candida-Epithelial Cell Interaction Distinguishes Colonization- versus Vulvovaginal Candidiasis- Associated Strains / Sala, Arianna; Ardizzoni, Andrea; Spaggiari, Luca; Vaidya, Nikhil; van der Schaaf, Jane; Rizzato, Cosmeri; Cermelli, Claudio; Mogavero, Selene; Krüger, Thomas; Himmel, Maximilian; Kniemeyer, Olaf; Brakhage, Axel A.; King, Benjamin L.; Lupetti, Antonella; Comar, Manola; de Seta, Francesco; Tavanti, Arianna; Blasi, Elisabetta; Wheeler, Robert T.; Pericolini, Eva. - In: MBIO. - ISSN 2161-2129. - 14:2(2023), pp. 1-18. [10.1128/mbio.00107-23]
Sala, Arianna; Ardizzoni, Andrea; Spaggiari, Luca; Vaidya, Nikhil; van der Schaaf, Jane; Rizzato, Cosmeri; Cermelli, Claudio; Mogavero, Selene; Krüger...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1298586
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