Anti-biofilm activity of sub-inhibitory povidone-iodine concentrations against Staphylococcus epidermidis and Staphylococcus aureus.

Biomaterial-related infections continue to hamper the success of reconstructive and arthroplasty procedures in orthopaedic surgery. Staphylococci are the most common etiologic agents, with biofilm formation representing a major virulence factor. Biofilms increase bacterial resistance to antimicrobial agents and host immune responses. In staphylococci, production of polysaccharide intercellular adhesin (PIA) by the enzyme products of the icaADBC operon is the best understood mechanism of biofilm development, making the ica genes a potential target for biofilm inhibitors. In this study we report that the antibacterial agent povidone-iodine (PI) also has anti-biofilm activity against Staphylococcus epidermidis and Staphylococcus aureus at sub-inhibitory concentrations (p < 0.001). Inhibition of biofilm by PI correlated with decreased transcription of the icaADBC operon, which in turn correlated with activation of the icaR transcriptional repressor in Staphylococcus epidermidis. These data reveal an additional therapeutic benefit of PI and suggest that studies to evaluate suitability of PI as biomaterial coating agent to reduce device-related infections are merited.

Hydrogen peroxide induced repression of icaADBC transcription and biofilm development in Staphylococcus epidermidis.

Expression of the icaADBC-encoded polysaccharide intercellular adhesion by Staphylococcus epidermidis promotes biofilm formation and represents an important virulence factor in biomaterial-related infections following orthopedic surgery. Biofilm development by the pathogen can be viewed as a protective reaction to environmental stressors including osmotic stress, thermal stress, and antimicrobial chemotherapy. Oxidative stress, arising from the release of toxic oxygen radicals by polymorphonuclear cells, is encountered by bacteria entering the body perioperatively. Evasion of this and other cell-mediated immune responses by pathogenic bacteria plays an important role in the development of chronic biomaterial-related infection. Here we investigated the impact of sublethal oxidative stress induced by H2O2 (<18 mM) on S. epidermidis biofilm formation. S. epidermidis grown in brain heart infusion (BHI) media supplemented with 5 mM H2O2 or 10 mM H2O2 formed significantly less biofilm (p < 0.01 and p < 0.001, respectively) than bacteria grown in BHI alone. Consistent with this, using reverse transcription-polymerase chain reaction expression of the ica locus was also shown to be reduced by subinhibitory concentrations of H2O2. Furthermore, diminished ica operon expression correlated with increased expression of icaR, which encodes a repressor of icaADBC. Thus, these data suggest that mild oxidative stress downregulates biofilm development by S. epidermidis and may have potential in a therapeutic context.