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

Abstract

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 H 2 O 2 (<18 mM) on S. epidermidis biofilm formation. S. epidermidis grown in brain heart infusion (BHI) media supplemented with 5 mM H 2 O 2 or 10 mM H 2 O 2 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 H 2 O 2 . 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. ß

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

“…These data are consistent with the role of icaR as a transcriptional repressor of the ica operon. 13,20 However the dramatic activation of icaR transcription in various PI concentrations was associated with a relatively modest decrease in icaADBC transcription indicating that PI can also influence ica operon expression and biofilm independently of icaR. Growth of S. epidermidis in H 2 O 2 has a smilar effect to PI 20 whereas exposure to 4% ethanol has the opposite effect leading to icaR repression and activation of icaADBC.…”

“…Determinations of MIC and minimum bacteriocidal concentration (MBC) were performed as previously described. 19,20 Biofilm Assays Semi-quantitative determinations of biofilm formation in 96-well tissue culture plates (Nunc, Denmark) using bacteria grown at 378C in BHI, and BHI supplemented with 0.17%, 0.35%, or 0.7% of PI were performed as described previously. [26][27][28] After overnight incubation at 378C, plates were washed three times with distilled H 2 O and dried for 1 h at 568C prior to staining adherent biofilm with a 0.4% crystal violet solution for 15 min.…”

“…19 In contrast, mild oxidative stress, induced by sub-inhibitory concentrations of hydrogen peroxide has been found to significantly reduce biofilm formation in S. epidermidis through down regulation of icaADBC operon expression. 20 Staphylococcus epidermidis is a skin commensal. This organism can exist on skin surface as micro-colonies that share similar properties of biofilms in terms of resistance to biocides.…”

Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model

“…aureus biofilm formation is a multifactorial process that progresses through coordinated phases. Particularly important is the early growth phase, when the bacterium strongly attaches to a substrate, which is mediated by cell surface factors that may include autolysin (51), teichoic acids (52), or polysaccharide intercellular adhesin (PIA), the product of the ica gene (53), whose expression promotes colonization and biofilm formation, especially during environmental stress (54,55) and in the course of a device-related infection (56). We found that np and NO-np significantly inhibited bacterial adhesion to plastic and glass surfaces.…”

Oxidation-sensing Regulator AbfR Regulates Oxidative Stress Responses, Bacterial Aggregation, and Biofilm Formation in Staphylococcus epidermidis

“…Oxidative stress inactivates AbfR, which acts as a repressor of abfR-SERP2195-gpxA operon. It has been shown that mild oxidative stress down-regulates S. epidermidis biofilm development (5,6,66). Similarly, we may speculate that oxidative stress acts as a signal to modulate S. epidermidis key virulence properties through AbfR.…”