The human pathogenic mold Aspergillus fumigatus is able to form a complex biofilm embedded in extracellular matrix. Biofilms confer antimicrobial resistance and it is well known that aspergillosis is often refractory to the conventional antifungal therapy. The treatment of biofilm-related infections poses a significant clinical challenge on a daily basis, promoting the search for new therapeutic agents. Our aim was to exploit the modulation of sphingolipid mediators as new therapeutic target to overcome antifungal resistance in biofilm-related infections. Antifungal susceptibility testing was performed on 20 clinical isolates of Aspergillus fumigatus and one reference strain (A. fumigatus Af293) according the EUCAST protocol. Sessile MICs were assessed on 24-h preformedbiofilm by means of XTT-reduction assay. Myriocin (0.25–64 mg/L), a commercial sphingolipid synthesis inhibitor, was used. The MEC50 value (mg/L) of Myriocin was 8 (range 4–16) for both planktonic and sessile cells. Drug-induced morphological alterations were analyzed by optical and electron microscopy (TEM) on 24h preformed A.fumigatus Af293 biofilms. An evident hyphal damage, resulting in short, stubby, and highly branched hyphae was observed by optical microscopy. At 24h, TEM studies showed important morphological alterations, such as invaginations of the cell membrane, modification in the vacuolar system and presence of multilamellar bodies, in some cases within vacuoles. The direct antifungal activity, observed on both planktonic and sessile fungi, suggests that inhibition of sphingolipid synthesis could represent a new target to fight biofilm-related A. fumigatus resistance

Antifungal activity of myriocin on clinically relevant aspergillus fumigatus strains producing biofilm / F. Perdoni, P. Signorelli, D. Cirasola, A. Caretti, V. Galimberti, M. Biggiogera, P. Gasco, C. Musicanti, G. Morace, E. Borghi. - In: BMC MICROBIOLOGY. - ISSN 1471-2180. - 15:(2015 Oct 30), pp. 248.1-248.8. [10.1186/s12866-015-0588-0]

Antifungal activity of myriocin on clinically relevant aspergillus fumigatus strains producing biofilm

F. Perdoni
Primo
;
P. Signorelli
Secondo
;
D. Cirasola;A. Caretti;G. Morace
Penultimo
;
E. Borghi
Ultimo
2015

Abstract

The human pathogenic mold Aspergillus fumigatus is able to form a complex biofilm embedded in extracellular matrix. Biofilms confer antimicrobial resistance and it is well known that aspergillosis is often refractory to the conventional antifungal therapy. The treatment of biofilm-related infections poses a significant clinical challenge on a daily basis, promoting the search for new therapeutic agents. Our aim was to exploit the modulation of sphingolipid mediators as new therapeutic target to overcome antifungal resistance in biofilm-related infections. Antifungal susceptibility testing was performed on 20 clinical isolates of Aspergillus fumigatus and one reference strain (A. fumigatus Af293) according the EUCAST protocol. Sessile MICs were assessed on 24-h preformedbiofilm by means of XTT-reduction assay. Myriocin (0.25–64 mg/L), a commercial sphingolipid synthesis inhibitor, was used. The MEC50 value (mg/L) of Myriocin was 8 (range 4–16) for both planktonic and sessile cells. Drug-induced morphological alterations were analyzed by optical and electron microscopy (TEM) on 24h preformed A.fumigatus Af293 biofilms. An evident hyphal damage, resulting in short, stubby, and highly branched hyphae was observed by optical microscopy. At 24h, TEM studies showed important morphological alterations, such as invaginations of the cell membrane, modification in the vacuolar system and presence of multilamellar bodies, in some cases within vacuoles. The direct antifungal activity, observed on both planktonic and sessile fungi, suggests that inhibition of sphingolipid synthesis could represent a new target to fight biofilm-related A. fumigatus resistance
No
English
fungal infections; ceramide; nanocarriers
Settore MED/07 - Microbiologia e Microbiologia Clinica
Articolo
Esperti anonimi
Ricerca di base
Pubblicazione scientifica
   Sphingolipid targeting in microbial infection and inflammation
   EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES - ESCMID
30-ott-2015
BioMed central
15
248
1
8
8
Pubblicato
Periodico con rilevanza internazionale
pubmed
Aderisco
info:eu-repo/semantics/article
Antifungal activity of myriocin on clinically relevant aspergillus fumigatus strains producing biofilm / F. Perdoni, P. Signorelli, D. Cirasola, A. Caretti, V. Galimberti, M. Biggiogera, P. Gasco, C. Musicanti, G. Morace, E. Borghi. - In: BMC MICROBIOLOGY. - ISSN 1471-2180. - 15:(2015 Oct 30), pp. 248.1-248.8. [10.1186/s12866-015-0588-0]
open
Prodotti della ricerca::01 - Articolo su periodico
10
262
Article (author)
Periodico con Impact Factor
F. Perdoni, P. Signorelli, D. Cirasola, A. Caretti, V. Galimberti, M. Biggiogera, P. Gasco, C. Musicanti, G. Morace, E. Borghi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/332666
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