Staphylococcus aureus is a leading pathogen in skin and skin structure infections, including surgical and traumatic infections that are associated with biofilm formation. Because biofilm formation is accompanied by high phenotypic resistance of the embedded bacteria, they are almost impossible to eradicate by conventional antibiotics. Therefore, alternative therapeutic strategies are of high interest. We generated nanostructured hybrid nonwovens via the electrospinning of a photoresponsive carbon monoxide (CO)-releasing molecule [CORM-1, Mn 2 (CO) 10 ] and the polymer polylactide. This nonwoven showed a CO-induced antimicrobial activity that was sufficient to reduce the biofilm-embedded bacteria by 70% after photostimulation at 405 nm. The released CO increased the concentration of reactive oxygen species (ROS) in the biofilms, suggesting that in addition to inhibiting the electron transport chain, ROS might play a role in the antimicrobial activity of CORMs on S. aureus. The nonwoven showed increased cytotoxicity on eukaryotic cells after longer exposure, most probably due to the released lactic acid, that might be acceptable for local and short-time treatments. Therefore, CO-releasing nonwovens might be a promising local antimicrobial therapy against biofilm-associated skin wound infections.
Staphylococcus aureus, both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA), is the leading pathogen in skin and skin structure infections (SSSIs), including surgical and traumatic infections (1, 2). S. aureus has developed a highly effective mechanism to invade tissues and evade the immune system by biofilm formation and intracellular persistence. This can result in chronic and recurring SSSI, particularly in patients with comorbidities such as diabetes mellitus (e.g., diabetic foot syndrome). Noneradicable S. aureus SSSI can be the focus of S. aureus bacteremia, which has a mortality of up to 30% (3). In the United States, community-acquired MRSA has emerged as one of the leading causes of community-acquired SSSI (2).Biofilms are sessile matrix-embedded microbial communities that colonize nearly all artificial and natural surfaces. They are thought to be present in more than 80% of all nosocomial bacterial infections (4). Compared to their planktonic counterparts, bacteria embedded in a biofilm benefit from the protective properties of the matrix, conveying up to 1,000-fold-higher resistance to antibiotics (5). The enhanced phenotypic resistance (correctly termed tolerance) of biofilms is caused mainly by decreased growth rates and metabolically inactive persister cells (a protected phenotypic state) (6). Most antibiotics inhibit metabolic processes in the cell, such as replication (e.g., fluoroquinolones), transcription (e.g., rifampin) or translation (e.g., aminoglycosides and macrolides), and therefore they become ineffective in these persister cells. Altered microenvironments (7) and enzymes hydrolyzing or modifying the antimicrobials that are enriched within the matrix are additio...