The effect of subminimal inhibitory concentrations of antibiotics on virulence factors expressed byStaphylococcus aureusbiofilms

Abstract

Aims: The effect of subminimal inhibitory concentrations (sub‐MICs) of cefalexin, ciprofloxacin and roxithromycin was investigated on some virulence factors [e.g. coagulase, Toxic Shock Syndrome Toxin 1 (TSST‐1) and biofilm formation] expressed by Staphylococcus aureus biofilms. Methods and Results: Biofilms were grown with and without the presence of 1/16 MIC of antibiotics on Sorbarod filters. Eluate supernatants were collected, and coagulase and TSST‐1 production were evaluated. Coagulase production was reduced in eluates exposed to roxithromycin when compared to control, while TSST‐1 production was reduced in biofilms exposed to cefalexin and to a lesser extent, ciprofloxacin. In addition, the ability of Staph. aureus to produce biofilm in microtitre plates in the presence of sub‐MIC antibiotics indicated that cefalexin induced biofilm formation at a wide range of sub‐MICs. TSST‐1 produced from the challenged and control biofilms was purified, and its proliferative activity was studied on single cell suspension of mouse splenocytes using MTS/PMS assay. No significant difference in the activity between the treated toxin and the control has been observed. Conclusions: Antibiotics at sub‐MIC levels interfere with bacterial biofilm virulence expression depending on the type and concentration of antibiotic used. Significance and Impact of the Study: The establishment of sub‐MICs of antibiotics in clinical situations may result in altered virulence states in pathogenic bacteria.

Effects of Low-Dose Amoxicillin on Staphylococcus aureus USA300 Biofilms

“…Previous studies showed that sub-MIC levels of ␤-lactam antibiotics induce biofilm formation in genetically diverse MRSA strains in vitro (16,28,(44)(45)(46). This process is of interest because it can provide information about biofilm regulation and the signaling pathways involved in global gene regulation in response to cell wall stress (16).…”

Extracellular DNA Impedes the Transport of Vancomycin in Staphylococcus epidermidis Biofilms Preexposed to Subinhibitory Concentrations of Vancomycin

“…Recent evidence has shown that subinhibitory concentrations of various antibiotics induced biofilm formation of S. epidermidis (2)(3)(4), which in part may explain some of the resistance to antibiotic therapy. In addition, although various antibiotics were able to reduce the biomass of S. epidermidis biofilms at sub-MICs, these biofilms exhibited an increased level of resistance to dicloxacillin, tetracycline, and rifampin (5).…”

“…Furthermore, despite high concentration levels in the surrounding environment, antibiotics at sub-MICs may exist in the internal parts of the biofilm, because of the physical and chemical barriers to the penetration of antibiotics provided by the biofilm matrix (3).…”

Influence of subinhibitory-concentration (sub-MIC) Cefetoxime on biofilm formation. SEM study of ESBL-producing Salmonella typhi

“…KR537433), have strongly demonstrated biofilm formation in the presence of cefetoxime (64 µg/ml) at sub-MIC but biofilm formation significantly dropped at MIC level (128 µg/ml) relatively forming weak biofilm. Several studies have reported antibiotic sub-MIC-induced biofilm formation in P. aeruginosa, K. pneumonia, E.coli, and S. aureus [40][41][42][43]. Significant biofilm formation in P. aeruginosa was demonstrated in response to tobramycin by Hoffman et al, [40].…”