N-Acetyl-L-cysteine and Cysteamine: New Strategies Against Mixed Biofilms of Non-encapsulated Streptococcus pneumoniae and Non-typeable Haemophilus influenzae [PublishAheadOfPrint]

Acute otitis media, a polymicrobial disease of the middle ear cavity of children, is a significant public health problem worldwide. It is most frequently caused by encapsulated Streptococcus pneumoniae and non-typeable Haemophilus influenzae, although the widespread use of pneumococcal conjugate vaccines is apparently producing an increase in carriage of non-encapsulated S. pneumoniae. Frequently, pneumococci and H. influenzae live together in the human nasopharynx forming a self-produced biofilm. Biofilms represent a global medical challenge since the inherent antibiotic resistance of their producers demands the use of high doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence. Here, we describe the development of an in vitro, non-encapsulated S. pneumoniae–non-typeable H. influenzae biofilm system using polystyrene or glass-bottom plates. Using confocal laser scanning microscopy and specific fluorescent labeling of pneumococcal cells with Helix pomatia agglutinin revealed an even distribution of both species within the biofilm. This simple and robust protocol of mixed biofilms has been used for testing the antimicrobial properties of two well known antioxidants that are widely used in the clinical setting, i.e., N-acetylcysteine and cysteamine. This repurposing approach showed the high potency of N-acetylcysteine and cysteamine against mixed biofilms of non-encapsulated S. pneumoniae and non-typeable H. influenzae. Decades of clinical use mean that these compounds are safe to use, which may accelerate their evaluation in humans.

http://ift.tt/2g3cCr5