Figure S3. UPGMA hierarchical clustering of C. parapsilosis genetic diversity calculated by using samplesâ distance similarities (Jaccard index) from RAPD genotyping. C. parapsilosis isolates from HC and RTT subjects in green and red, respectively. (PDF 15Â kb

Antonio CalabrĂ˛ (3490550)

Carlotta De Filippo (713585)

Claudio De Felice (383430)

Claudio Donati (66818)

Daniela Renzi (1656148)

Duccio Cavalieri (148329)

Francesco Strati (133937)

Joussef Hayek (383435)

Lisa Rizzetto (148311)

Olivier Jousson (281189)

Silvia Leoncini (383432)

BMC Gastroenterology

Abstract Background Rett syndrome (RTT) is a neurological disorder mainly caused by mutations in MeCP2 gene. It has been shown that MeCP2 impairments can lead to cytokine dysregulation due to MeCP2 regulatory role in T-helper and T-reg mediated responses, thus contributing to the pro-inflammatory status associated with RTT. Furthermore, RTT subjects suffer from an intestinal dysbiosis characterized by an abnormal expansion of the Candida population, a known factor responsible for the hyper-activation of pro-inflammatory immune responses. Therefore, we asked whether the intestinal fungal population of RTT subjects might contribute the sub-inflammatory status triggered by MeCP2 deficiency. Methods We evaluated the cultivable gut mycobiota from a cohort of 50 RTT patients and 29 healthy controls characterizing the faecal fungal isolates for their virulence-related traits, antifungal resistance and immune reactivity in order to elucidate the role of fungi in RTT’s intestinal dysbiosis and gastrointestinal physiology. Results Candida parapsilosis, the most abundant yeast species in RTT subjects, showed distinct genotypic profiles if compared to healthy controls’ isolates as measured by hierarchical clustering analysis from RAPD genotyping. Their phenotypical analysis revealed that RTT’s isolates produced more biofilm and were significantly more resistant to azole antifungals compared to the isolates from the healthy controls. In addition, the high levels of IL-1β and IL-10 produced by peripheral blood mononuclear cells and the mixed Th1/Th17 cells population induced by RTT C. parapsilosis isolates suggest the capacity of these intestinal fungi to persist within the host, being potentially involved in chronic, pro-inflammatory responses. Conclusions Here we demonstrated that intestinal C. parapsilosis isolates from RTT subjects hold phenotypic traits that might favour the previously observed low-grade intestinal inflammatory status associated with RTT. Therefore, the presence of putative virulent, pro-inflammatory C. parapsilosis strains in RTT could represent an additional factor in RTT’s gastrointestinal pathophysiology, whose mechanisms are not yet clearly understood

Francesco Strati

Antonio Calabrò

Claudio Donati

Claudio De Felice

Joussef Hayek

Olivier Jousson

Silvia Leoncini

Daniela Renzi

Lisa Rizzetto

Carlotta De Filippo

Duccio Cavalieri

Directory of Open Access Journals

Intestinal Candida parapsilosis isolates from Rett syndrome subjects bear potential virulent traits and capacity to persist within the host

Background: Rett syndrome (RTT) is a neurological disorder mainly caused by mutations in MeCP2 gene. It has
been shown that MeCP2 impairments can lead to cytokine dysregulation due to MeCP2 regulatory role in T-helper
and T-reg mediated responses, thus contributing to the pro-inflammatory status associated with RTT. Furthermore,
RTT subjects suffer from an intestinal dysbiosis characterized by an abnormal expansion of the Candida population,
a known factor responsible for the hyper-activation of pro-inflammatory immune responses. Therefore, we asked
whether the intestinal fungal population of RTT subjects might contribute the sub-inflammatory status triggered by
MeCP2 deficiency.
Methods: We evaluated the cultivable gut mycobiota from a cohort of 50 RTT patients and 29 healthy controls
characterizing the faecal fungal isolates for their virulence-related traits, antifungal resistance and immune reactivity
in order to elucidate the role of fungi in RTT’s intestinal dysbiosis and gastrointestinal physiology.
Results: Candida parapsilosis, the most abundant yeast species in RTT subjects, showed distinct genotypic profiles if
compared to healthy controls’ isolates as measured by hierarchical clustering analysis from RAPD genotyping. Their
phenotypical analysis revealed that RTT’s isolates produced more biofilm and were significantly more resistant to
azole antifungals compared to the isolates from the healthy controls. In addition, the high levels of IL-1β and IL-10
produced by peripheral blood mononuclear cells and the mixed Th1/Th17 cells population induced by RTT C.
parapsilosis isolates suggest the capacity of these intestinal fungi to persist within the host, being potentially
involved in chronic, pro-inflammatory responses.
Conclusions: Here we demonstrated that intestinal C. parapsilosis isolates from RTT subjects hold phenotypic traits
that might favour the previously observed low-grade intestinal inflammatory status associated with RTT. Therefore,
the presence of putative virulent, pro-inflammatory C. parapsilosis strains in RTT could represent an additional factor
in RTT’s gastrointestinal pathophysiology, whose mechanisms are not yet clearly understood

Strati, F.

Calabrò, A.

Donati, C.

De Felice, C.

Hayek, J.

Jousson, O.

Leoncini S.

Renzi D.

Rizzetto, L.

De Filippo, C.

Cavalieri, D.

Archivio istituzionale della ricerca - Fondazione Edmund Mach

Strati, Francesco

Calabr&#242

Donati, Claudio

De Felice, Claudio

Hayek, Joussef

Jousson, Olivier

Leoncini, Silvia

Renzi, Daniela

Rizzetto, Lisa

De Filippo, Carlotta

Cavalieri, Duccio

Florence Research

English

Figure S4. UPGMA hierarchical clustering of C. albicans genetic diversity calculated by using samplesâ distance similarities (Jaccard index) from RAPD genotyping. C. albicans isolates from HC and RTT subjects in green and red, respectively; in gray the lab strain SC5314. (PDF 16Â kb

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Additional file 5: of Intestinal Candida parapsilosis isolates from Rett syndrome subjects bear potential virulent traits and capacity to persist within the host