Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms pre-exposed to sub-inhibitory concentrations of vancomycin
Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms pre-exposed to sub-inhibitory concentrations of vancomycin
Staphylococcus epidermidis biofilm formation is responsible for the persistence of orthopaedic implant infections. Previous studies have shown that exposure of S. epidermidis biofilms to sub-minimum inhibitory concentrations (sub-MIC) of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC vancomycin treated S. epidermidis biofilms was impeded, when compared to control, untreated biofilms. Further experiments showed an increase in the eDNA concentration in biofilms pre-exposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added, S. epidermidis DNA increased planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (iTC) revealed that the binding constant of DNA and vancomycin was 100-fold higher, than the previously reported, binding constant of vancomycin and its intended cellular D-Ala-D-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC vancomycin treated S. epidermidis biofilms, which might be an important factor for the persistence of biofilm infections.
Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms pre-exposed to sub-inhibitory concentrations of vancomycin
7273-7282
Doroshenko, N.
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Tseng, B. S.
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Howlin, R. P.
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Deacon, J.
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Wharton, J. A.
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Thurner, P. J.
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Gilmore, B. F.
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Parsek, M. R.
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Stoodley, P.
08614665-92a9-4466-806e-20c6daeb483f
December 2014
Doroshenko, N.
6a7a1607-b199-4700-a6a1-b5a35ad57348
Tseng, B. S.
c9a51172-e139-433a-9841-9bca8344dac3
Howlin, R. P.
8b128b91-cf1e-4e77-a1b8-bc80dd829d8e
Deacon, J.
e4136637-8269-4263-b6ca-b3ce794bade3
Wharton, J. A.
965a38fd-d2bc-4a19-a08c-2d4e036aa96b
Thurner, P. J.
ab711ddd-784e-48de-aaad-f56aec40f84f
Gilmore, B. F.
aa0f36cf-fd0b-40be-a3ca-11f6bfc5bc53
Parsek, M. R.
2125f1a7-8947-4337-8c62-05573b700a68
Stoodley, P.
08614665-92a9-4466-806e-20c6daeb483f
Doroshenko, N., Tseng, B. S., Howlin, R. P., Deacon, J., Wharton, J. A., Thurner, P. J., Gilmore, B. F., Parsek, M. R. and Stoodley, P.
(2014)
Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms pre-exposed to sub-inhibitory concentrations of vancomycin.
Antimicrobial Agents and Chemotherapy, 58 (12), .
(doi:10.1128/AAC.03132-14).
Abstract
Staphylococcus epidermidis biofilm formation is responsible for the persistence of orthopaedic implant infections. Previous studies have shown that exposure of S. epidermidis biofilms to sub-minimum inhibitory concentrations (sub-MIC) of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC vancomycin treated S. epidermidis biofilms was impeded, when compared to control, untreated biofilms. Further experiments showed an increase in the eDNA concentration in biofilms pre-exposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added, S. epidermidis DNA increased planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (iTC) revealed that the binding constant of DNA and vancomycin was 100-fold higher, than the previously reported, binding constant of vancomycin and its intended cellular D-Ala-D-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC vancomycin treated S. epidermidis biofilms, which might be an important factor for the persistence of biofilm infections.
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e-pub ahead of print date: 29 September 2014
Published date: December 2014
Keywords:
Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms pre-exposed to sub-inhibitory concentrations of vancomycin
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nCATS Group
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Local EPrints ID: 370063
URI: http://eprints.soton.ac.uk/id/eprint/370063
ISSN: 0066-4804
PURE UUID: 5e3f3b9a-2c25-4fc0-9f41-d27d8660aef0
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Date deposited: 15 Oct 2014 12:22
Last modified: 15 Mar 2024 03:34
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Author:
N. Doroshenko
Author:
B. S. Tseng
Author:
R. P. Howlin
Author:
J. Deacon
Author:
B. F. Gilmore
Author:
M. R. Parsek
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