Targeted inhibition of methicillin-resistant Staphylococcus aureus biofilm formation by a graphene oxide-loaded aptamer/berberine bifunctional complex

Abstract

Biofilm formation is known to promote drug resistance in methicillin-resistant Staphylococcus aureus (MRSA), which is closely related to persistent infections in hospital settings. In this study, a DNA aptamer specific to penicillin-binding protein 2a (PBP2a) with a dissociation constant ( K d ) of 82.97 ± 8.86 nM was obtained after 14 cycles of systematic evolution of ligands by exponential enrichment (SELEX). Next, a bifunctional complex containing the aptamer intercalated by berberine into the double-strand region was prepared and adsorbed onto the surface of graphene oxide ( GO) by π-stacking interactions. The GO-loaded aptamer/berberine bifunctional complex showed significantly higher inhibition of MRSA biofilm formation than the control. Furthermore, this study shows that the complex possesses anti-biofilm activity, which can be attributed to the ability of the aptamer to reduce cell-surface attachment by blocking the function of PBP2a and berberine to attenuate the level of the accessory gene regulator ( agr ) system, which plays an important role in mediating MRSA biofilm formation. Therefore, the simultaneous delivery of berberine and PBP2a-targted aptamer using GO may have potential for the treatment of chronic infections caused by MRSA biofilms. It also provides a new avenue for multitarget treatment of bacterial biofilms.

Understanding bacterial biofilms: From definition to treatment strategies

“…Sengupta et al (2020) reported the effectiveness of aptamer-DNA template silver nanocluster (Ag-NC) for inhibiting P. aeruginosa biofilm formation, and Ag-NC as a sensor is expected to be a new way to detect planktonic cells and biofilm formation. Ning et al (2022) found that simultaneous delivery of penicillin-binding protein 2aspecific DNA aptamer and berberine via graphene oxide effectively inhibited the formation of MRSA biofilms, and this complex could potentially be an effective strategy for the treatment of chronic infections caused by MRSA biofilms. P. gingivalis can cause the occurrence of periodontitis.…”

Recent advances on the regulation of bacterial biofilm formation by herbal medicines

“…As such, berberine exerted synergistic effects on inhibiting Candida albicans / S. aureus dual strain biofilms in combination with amphotericin B, an efficient antibiotic that utilized for the treatment of fungal infections in clinic ( Gao et al, 2021 ). A study by Ning et al demonstrated that berberine inhibited biofilm formation via downregulation of the expression of the QS regulatory gene agrA in a concentration-dependent manner in S. aureus ( Ning et al, 2022 ). Moreover, Ferrazzano et al found that berberine exerted efficient antimicrobial efficacy against diverse endodontic pathogens including Fusobacterium nucleatum , Prevotella intermedia , and Enterococcus faecalis ( Ferrazzano et al, 2011 ).…”

A fluorometric graphene oxide-based assay for determination of agrB gene transcription in methicillin-resistant Staphylococcus aureus by coupling exonuclease III-assisted target recycling and hybridization chain reaction

“…The agrB gene encodes a processor protein that mediates the cyclization of an autoinducing peptide (AIP), which triggers biofilm formation. 5 Therefore, the determination of agrB gene expression can not only monitor the dynamic process of biofilm formation in MRSA but also study the possible molecular mechanisms of drug action.…”