The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase
Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against S. aureus biofilms grown in vitro (96-well plates or catheters) and in viv...
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Published in | Nature communications Vol. 7; no. 1; p. 13286 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
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Nature Publishing Group UK
03.11.2016
Nature Publishing Group Nature Portfolio |
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Abstract | Biofilms play a major role in
Staphylococcus aureus
pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against
S. aureus
biofilms grown
in vitro
(96-well plates or catheters) and
in vivo
(murine model of implanted catheters). The degree of synergy among different clinical isolates is inversely proportional to the expression level of
ica
operon, the products of which synthesize poly-
N
-acetyl-glucosamine polymers, a major constituent of biofilm matrix.
In vitro,
caspofungin inhibits the activity of IcaA, which shares homology with β-1-3-glucan synthase (caspofungin’s pharmacological target in fungi). This inhibition destructures the matrix, reduces the concentration and polymerization of exopolysaccharides in biofilms, and increases fluoroquinolone penetration inside biofilms. Our study identifies a bacterial target for caspofungin and indicates that IcaA inhibitors could potentially be useful in the treatment of biofilm-related infections.
Biofilms formed by
Staphylococcus aureus
are poorly responsive to antibiotics. Here, Siala
et al
. show that an antifungal drug (caspofungin) enhances the activity of fluoroquinolone antibiotics against S. aureus biofilms by inhibiting an enzyme involved in synthesis of the biofilm matrix. |
---|---|
AbstractList | Biofilms play a major role in
Staphylococcus aureus
pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against
S. aureus
biofilms grown
in vitro
(96-well plates or catheters) and
in vivo
(murine model of implanted catheters). The degree of synergy among different clinical isolates is inversely proportional to the expression level of
ica
operon, the products of which synthesize poly-
N
-acetyl-glucosamine polymers, a major constituent of biofilm matrix.
In vitro,
caspofungin inhibits the activity of IcaA, which shares homology with β-1-3-glucan synthase (caspofungin's pharmacological target in fungi). This inhibition destructures the matrix, reduces the concentration and polymerization of exopolysaccharides in biofilms, and increases fluoroquinolone penetration inside biofilms. Our study identifies a bacterial target for caspofungin and indicates that IcaA inhibitors could potentially be useful in the treatment of biofilm-related infections.
Biofilms formed by
Staphylococcus aureus
are poorly responsive to antibiotics. Here, Siala
et al
. show that an antifungal drug (caspofungin) enhances the activity of fluoroquinolone antibiotics against S. aureus biofilms by inhibiting an enzyme involved in synthesis of the biofilm matrix. Biofilms formed byStaphylococcus aureus are poorly responsive to antibiotics. Here, Siala et al. show that an antifungal drug (caspofungin) enhances the activity of fluoroquinolone antibiotics against S. aureus biofilms by inhibiting an enzyme involved in synthesis of the biofilm matrix. Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against S. aureus biofilms grown in vitro (96-well plates or catheters) and in vivo (murine model of implanted catheters). The degree of synergy among different clinical isolates is inversely proportional to the expression level of ica operon, the products of which synthesize poly-N-acetyl-glucosamine polymers, a major constituent of biofilm matrix. In vitro, caspofungin inhibits the activity of IcaA, which shares homology with β-1-3-glucan synthase (caspofungin's pharmacological target in fungi). This inhibition destructures the matrix, reduces the concentration and polymerization of exopolysaccharides in biofilms, and increases fluoroquinolone penetration inside biofilms. Our study identifies a bacterial target for caspofungin and indicates that IcaA inhibitors could potentially be useful in the treatment of biofilm-related infections. Abstract Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against S. aureus biofilms grown in vitro (96-well plates or catheters) and in vivo (murine model of implanted catheters). The degree of synergy among different clinical isolates is inversely proportional to the expression level of ica operon, the products of which synthesize poly- N -acetyl-glucosamine polymers, a major constituent of biofilm matrix. In vitro, caspofungin inhibits the activity of IcaA, which shares homology with β-1-3-glucan synthase (caspofungin’s pharmacological target in fungi). This inhibition destructures the matrix, reduces the concentration and polymerization of exopolysaccharides in biofilms, and increases fluoroquinolone penetration inside biofilms. Our study identifies a bacterial target for caspofungin and indicates that IcaA inhibitors could potentially be useful in the treatment of biofilm-related infections. |
ArticleNumber | 13286 |
Author | Van Dijck, Patrick Van Bambeke, Françoise Tulkens, Paul M Vleugels, Jef Braem, Annabel Kucharíková, Soňa Mingeot-Leclercq, Marie-Paule Siala, Wafi |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27808087$$D View this record in MEDLINE/PubMed |
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Snippet | Biofilms play a major role in
Staphylococcus aureus
pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the... Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the... Abstract Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin... Biofilms formed byStaphylococcus aureus are poorly responsive to antibiotics. Here, Siala et al. show that an antifungal drug (caspofungin) enhances the... |
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StartPage | 13286 |
SubjectTerms | 14/19 14/28 14/34 38/1 38/23 38/5 631/154/436/2388 631/154/555 631/326/46 64/60 Antibiotics Bacteria Catheters Humanities and Social Sciences multidisciplinary Nosocomial infections Polymerization Proteins Science Science (multidisciplinary) Staphylococcus infections |
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Title | The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase |
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