In Vitro Antimicrobial Efficacy of Tobramycin Against Staphylococcus aureus Biofilms in Combination With or Without DNase I and/or Dispersin B: A Preliminary Investigation

Abstract

Staphylococcus aureus in biofilms is highly resistant to the treatment with antibiotics, to which the planktonic cells are susceptible. This is likely to be due to the biofilm creating a protective barrier that prevents antibiotics from accessing the live pathogens buried in the biofilm. S. aureus biofilms consist of an extracellular matrix comprising, but not limited to, extracellular bacterial DNA (eDNA) and poly-β-1, 6-N-acetyl-d-glucosamine (PNAG). Our study revealed that despite inferiority of dispersin B (an enzyme that degrades PNAG) to DNase I that cleaves eDNA, in dispersing the biofilm of S. aureus, both enzymes were equally efficient in enhancing the antibacterial efficiency of tobramycin, a relatively narrow-spectrum antibiotic against infections caused by gram-positive and gram-negative pathogens, including S. aureus, used in this investigation. However, a combination of these two biofilm-degrading enzymes was found to be significantly less effective in enhancing the antimicrobial efficacy of tobramycin than the individual application of the enzymes. These findings indicate that combinations of different biofilm-degrading enzymes may compromise the antimicrobial efficacy of antibiotics and need to be carefully assessed in vitro before being used for treating medical devices or in pharmaceutical formulations for use in the treatment of chronic ear or respiratory infections.

Activity of Antibiotics against Staphylococcus aureus in an In Vitro Model of Biofilms in the Context of Cystic Fibrosis: Influence of the Culture Medium

“…Regarding the relative potency, we noticed that a reduction of 33% of metabolic activity or of 1 log 10 CFU was rarely reached in ASM and at drug concentrations that were higher than those in TGN or than the MIC measured for planktonic cultures. Although these effects do not strictly correspond to bacteriostasis, our results confirm that higher concentrations of antibiotics are needed to act against biofilms than against planktonic cultures (14,18,(22)(23)(24)(31)(32)(33)(34)(35). The low penetration and/or bioavailability of antibiotics in the biofilm matrix is probably a main reason for this loss in potency (3,4,18) and may become even more critical in ASM.…”

Lipoteichoic Acid Inhibits Staphylococcus aureus Biofilm Formation

“…In addition, we also showed that Lp.LTA induced bacterial dispersion from pre-formed biofilm of S. aueus . Biofilm dispersing agents, such as Dispersin B, chitosan, and glycoside hydrolases, have been reported to release planktonic cells that are more susceptible to antibiotics than bacterial cells shielded by biofilm ( Orgaz et al, 2011 ; Fleming et al, 2017 ; Waryah et al, 2017 ). Therefore, Lp.LTA may also act as a dispersing agent to potentiate antibiotic activity.…”

Extracellular polymeric substance (EPS)-degrading enzymes reduce staphylococcal surface attachment and biocide resistance on pig skin in vivo

“…For example, one recent study showed that a combination of DNase I and dispersin B was significantly less effective in enhancing the antimicrobial efficacy of tobramycin against S . aureus than the individual enzymes alone [ 43 ]. However, a combination of DNase I and dispersin B did exhibit additive biofilm inhibiting activity against S .…”