Clearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-l-cysteine and cysteamine

Abstract Biofilm-associated infections are of great concern because they are associated with antibiotic resistance and immune evasion. Co-colonization by Staphylococcus aureus and Streptococcus pneumoniae is possible and a threat in clinical practice. We investigated the interaction between S. aureu...

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Main Authors: Julio Sempere, Mirella Llamosí, Federico Román, Darío Lago, Fernando González-Camacho, Covadonga Pérez-García, Jose Yuste, Mirian Domenech
Format: Article
Language:English
Published: Nature Portfolio 2022-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-10609-x
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author Julio Sempere
Mirella Llamosí
Federico Román
Darío Lago
Fernando González-Camacho
Covadonga Pérez-García
Jose Yuste
Mirian Domenech
author_facet Julio Sempere
Mirella Llamosí
Federico Román
Darío Lago
Fernando González-Camacho
Covadonga Pérez-García
Jose Yuste
Mirian Domenech
author_sort Julio Sempere
collection DOAJ
description Abstract Biofilm-associated infections are of great concern because they are associated with antibiotic resistance and immune evasion. Co-colonization by Staphylococcus aureus and Streptococcus pneumoniae is possible and a threat in clinical practice. We investigated the interaction between S. aureus and S. pneumoniae in mixed biofilms and tested new antibiofilm therapies with antioxidants N-acetyl-l-cysteine (NAC) and cysteamine (Cys). We developed two in vitro S. aureus–S. pneumoniae mixed biofilms in 96-well polystyrene microtiter plates and we treated in vitro biofilms with Cys and NAC analyzing their effect by CV staining and viable plate counting. S. pneumoniae needed a higher proportion of cells in the inoculum and planktonic culture to reach a similar population rate in the mixed biofilm. We demonstrated the effect of Cys in preventing S. aureus biofilms and S. aureus–S. pneumoniae mixed biofilms. Moreover, administration of 5 mg/ml of NAC nearly eradicated the S. pneumoniae population and killed nearly 94% of MSSA cells and 99% of MRSA cells in the mixed biofilms. The methicillin resistance background did not change the antioxidants effect in S. aureus. These results identify NAC and Cys as promising repurposed drug candidates for the prevention and treatment of mixed biofilms by S. pneumoniae and S. aureus.
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spelling doaj.art-30d7b219c41145e4aab8316d4115f5612022-12-22T01:46:51ZengNature PortfolioScientific Reports2045-23222022-04-0112111210.1038/s41598-022-10609-xClearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-l-cysteine and cysteamineJulio Sempere0Mirella Llamosí1Federico Román2Darío Lago3Fernando González-Camacho4Covadonga Pérez-García5Jose Yuste6Mirian Domenech7Spanish Pneumococcal Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos IIISpanish Pneumococcal Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos IIIIntrahospital Infections Unit, National Centre for Microbiology, Instituto de Salud Carlos IIISpanish Pneumococcal Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos IIISpanish Pneumococcal Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos IIISpanish Pneumococcal Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos IIISpanish Pneumococcal Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos IIISpanish Pneumococcal Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos IIIAbstract Biofilm-associated infections are of great concern because they are associated with antibiotic resistance and immune evasion. Co-colonization by Staphylococcus aureus and Streptococcus pneumoniae is possible and a threat in clinical practice. We investigated the interaction between S. aureus and S. pneumoniae in mixed biofilms and tested new antibiofilm therapies with antioxidants N-acetyl-l-cysteine (NAC) and cysteamine (Cys). We developed two in vitro S. aureus–S. pneumoniae mixed biofilms in 96-well polystyrene microtiter plates and we treated in vitro biofilms with Cys and NAC analyzing their effect by CV staining and viable plate counting. S. pneumoniae needed a higher proportion of cells in the inoculum and planktonic culture to reach a similar population rate in the mixed biofilm. We demonstrated the effect of Cys in preventing S. aureus biofilms and S. aureus–S. pneumoniae mixed biofilms. Moreover, administration of 5 mg/ml of NAC nearly eradicated the S. pneumoniae population and killed nearly 94% of MSSA cells and 99% of MRSA cells in the mixed biofilms. The methicillin resistance background did not change the antioxidants effect in S. aureus. These results identify NAC and Cys as promising repurposed drug candidates for the prevention and treatment of mixed biofilms by S. pneumoniae and S. aureus.https://doi.org/10.1038/s41598-022-10609-x
spellingShingle Julio Sempere
Mirella Llamosí
Federico Román
Darío Lago
Fernando González-Camacho
Covadonga Pérez-García
Jose Yuste
Mirian Domenech
Clearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-l-cysteine and cysteamine
Scientific Reports
title Clearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-l-cysteine and cysteamine
title_full Clearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-l-cysteine and cysteamine
title_fullStr Clearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-l-cysteine and cysteamine
title_full_unstemmed Clearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-l-cysteine and cysteamine
title_short Clearance of mixed biofilms of Streptococcus pneumoniae and methicillin-susceptible/resistant Staphylococcus aureus by antioxidants N-acetyl-l-cysteine and cysteamine
title_sort clearance of mixed biofilms of streptococcus pneumoniae and methicillin susceptible resistant staphylococcus aureus by antioxidants n acetyl l cysteine and cysteamine
url https://doi.org/10.1038/s41598-022-10609-x
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