Clearance of mixed bioflms of Streptococcus pneumoniae and methicillin‑susceptible/resistant Staphylococcus aureus by antioxidants N‑acetyl‑l‑cysteine and cysteamine.

Abstract

Bioflm-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 bioflms and tested new antibioflm therapies with antioxidants N-acetyl-l-cysteine (NAC) and cysteamine (Cys). We developed two in vitro S. aureus–S. pneumoniae mixed bioflms in 96-well polystyrene microtiter plates and we treated in vitro bioflms with Cys and NAC analyzing their efect 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 bioflm. We demonstrated the efect of Cys in preventing S. aureus bioflms and S. aureus–S. pneumoniae mixed bioflms. 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 bioflms. The methicillin resistance background did not change the antioxidants efect in S. aureus. These results identify NAC and Cys as promising repurposed drug candidates for the prevention and treatment of mixed bioflms by S. pneumoniae and S. aureus.