Quaternized Chitosan Inhibits icaA Transcription and Biofilm Formation by Staphylococcus on a Titanium Surface

Abstract

Our previous study (Z. X. Peng et al., Carbohydr. Polym. 81:275-283, 2010) demonstrated that water-soluble quaternary ammonium salts, which are produced by the reaction of chitosan with glycidyl trimethylammonium chloride, provide chitosan derivatives with enhanced antibacterial ability. Because biofilm formation is believed to comprise the key step in the development of orthopedic implant-related infections, we further evaluated the efficacy of hydroxypropyltrimethyl ammonium chloride chitosan (HACC) with different degrees of substitution (DS; referred to as HACC 6%, 18%, and 44%) in preventing biofilm formation on a titanium surface. We used a tissue culture plate method to quantify the biomass of Staphylococcus epidermidis and Staphylococcus aureus biofilms and found that HACC, especially HACC 18% and 44%, significantly inhibited biofilm formation compared to the untreated control, even at concentrations far below their MICs (P < 0.05). Scanning electron microscopy showed that inhibition of biofilm formation on titanium increased dramatically with increased DS and HACC concentrations. Confocal laser scanning microscopy indicated that growth of a preexisting biofilm on titanium was inhibited by concentrations of HACC 18% and 44% below their minimum biofilm eradication concentrations. We also demonstrated that HACC inhibited the expression of icaA, which mediates the production of extracellular polysaccharides, both in new biofilms and in preexisting biofilms on titanium. Our results indicate that HACC may serve as a new antibacterial agent to inhibit biofilm formation and prevent orthopedic implant-related infections.

In Vivo Effect of Quaternized Chitosan-Loaded Polymethylmethacrylate Bone Cement on Methicillin-Resistant Staphylococcus epidermidis Infection of the Tibial Metaphysis in a Rabbit Model

“…For multidrug-resistant bacteria, however, particularly gentamicin-resistant bacteria, gentamicin-loaded PMMA has proven inadequate for treating or preventing infections. As reported in our previous work, HACC with 26% DS in PMMA bone cements exhibited predictable release kinetics and antibacterial activity for staphylococci (19,20). In the present study, we further demonstrate the effectiveness of HACC-loaded PMMA in treating bacterial infections in the tibial metaphysis in an animal model.…”

“…To improve the antibacterial activity and solubility of chitosan, quaternary ammonium chitosan derivatives have been synthesized, and their antibacterial activities have demonstrated significant increases with increasing alkyl substituent chain length (17)(18)(19)(20)(21). We synthesized a new quaternized chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan [HACC]) that contains a series of quaternary ammonium substitutions, and we found that the antibacterial activities of HACC were enhanced as the quaternary ammonium degree of substitution (DS) increased (18)(19)(20). In vitro studies demonstrated that HACC-loaded PMMA (PMMA-H) bone cement exhibited strong antibacterial activity and good biocompatibility with osteogenic cells (20,21).…”

Activity of Gallidermin on Staphylococcus aureus and Staphylococcus epidermidis Biofilms

“…There are many reports on the activities of natural compounds on staphylococcal biofilm formation. Hydroxypropyltrimethyl ammonium chloride chitosan inhibits biofilm formation as well as expression of the icaA gene (40). Providone iodine also inhibits biofilm formation and decreases transcription of the ica operon (38).…”

Inhibited bacterial biofilm formation and improved osteogenic activity on gentamicin-loaded titania nanotubes with various diameters

“…A standard curve with known concentrations of gentamicin (Sigma-Aldrich) was used to determine the unknown concentrations. [21][22][23] Our previous study demonstrated that the three tested strains were biofilm-producing bacterial strains. 21,24 Bacterial adhesion assay using the spread plate method…”