In vitro activities of different inhibitors of bacterial transcription against Staphylococcus epidermidis biofilm

Abstract

Staphylococcus epidermidis is a major cause of nosocomial infections because of its ability to form biofilms on the surface of medical devices. Only a few antibacterial agents are relatively active against biofilms, and rifampin, a transcription inhibitor, ranks among the most effective molecules against biofilm-related infections. Whether this efficacy is due to advantageous structural properties of rifampin or to the fact that the RNA polymerase is a favorable target remains unclear. In an attempt to answer this question, we investigated the action of different transcription inhibitors against S. epidermidis biofilm, including the newest synthetic transcription inhibitors. This comparison suggests that most of the antibiotics that target the RNA polymerase are active on S. epidermidis biofilms at concentrations close to their MICs. One of these compounds, CBR703, despite its high MIC ranks among the best antibiotics to eradicate biofilm-embedded bacteria.

FIG. 1.

Chemical structures of rifampin (a), rifapentine (b), rifaximin (c), streptolydigin (d), lipiarmycin (e), thiolutin (f), holomycin (g), CBR703 (h), CBR64 (i), SB2 (j), and ureidothiophene (k).

FIG. 2.

Correlation curves between the ATP-counting luminescence values and the amount of biofilm-embedded S. epidermidis bacteria. (A) 24-h biofilm; (B) 48-h biofilm. The mean value ± the standard error is shown.

FIG. 3.

Difference of S. epidermidis counts in log₁₀ (CFU/well) between unchallenged and challenged 24-h biofilms as measured by bioluminescence. Challenged biofilms were exposed for 24 h to the transcription inhibitors at concentrations ranging from 1× MIC to 16× MIC. The mean bacterial amount within the unchallenged biofilm was 6.55 ± 0.02 log₁₀ CFU/well. The dashed line represents the difference of counts after challenge with ciprofloxacin at 20 μg/ml for 24 h. The mean value of the bacterial count ± the standard error is given. RIF, rifampin; RFP, rifapentine; RFX, rifaximin; STL, streptolydigin; LIP, lipiarmycin; THL, thiolutin; HOL, holomycin; URT, ureidothiophene.