Abstract
This study aims to investigate the antimicrobial and antibiofilm activity of berberine chloride (BBR) and vancomycin (VAN) as well as synergistic combinations of BBR with VAN against Clostridioides difficile strains. The effect of different concentrations of BBR on strain motility was also assessed. Twelve C. difficile strains (two reference C. difficile 630, ATCC 9689, and one control M120, and 9 clinical C. difficile strains belonging to the PCR-ribotype (RT027)) were collected and investigated for their susceptibility to BBR and VAN in planktonic and biofilm forms. Both the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of BBR for the C. difficile strains were found to vary over a broad range (256–1.024 mg/L and 256–16.384 mg/L, respectively). The MIC and MBC of VAN also varied greatly, ranging from 0.25 to 4.0 mg/L for MIC and 0.25 to 64.0 mg/L for MBC. The synergistic effect of the sub-MIC (1/2 MIC) BBR with VAN reduced of MICs of VAN against the planktonic forms of ten C. difficile strains. The sub-MIC of BBR enhanced the biofilm formation of one strain and was found to be statistically significant. In addition, the sub-MIC of BBR with VAN surprisingly enhanced the biofilm formation of one C. difficile strain. The effect of inhibition of motility in the presence of BBR was statistically significant for 3 clinical strains (p < 0.05). Altogether, BBR exhibited strong antimicrobial activity against C. difficile, and the analysis of the combination of BBR with VAN showed a synergistic effect.
Highlights
Clostridioides difficile is one of the most common multi-drug-resistant organisms in hospital-acquired infections and is associated with high morbidity and mortality [1,2,3]
The synergistic effect of the sub-minimum inhibitory concentration (MIC) (1/2 MIC) Berberine chloride (BBR) with VAN reduced of MICs of VAN against the planktonic forms of ten C. difficile strains
We investigated the antimicrobial and antibiofilm activity of synergistic combinations of berberine (BBR) and vancomycin (VAN) against C. difficile strains and the activity of BBR and VAN individually, as well as the effect of different concentrations of BBR on strain motility
Summary
Clostridioides difficile (formerly Clostridium difficile) is one of the most common multi-drug-resistant organisms in hospital-acquired infections and is associated with high morbidity and mortality [1,2,3]. The main virulent factors of C. difficile are two toxins: toxin A (TcdA) and toxin B (TcdB). These virulence factors are glycosyltransferases that inactivate Rho, Ras, and Rac (GTP-binding proteins), resulting in the damage of the colonic epithelium and, subsequently, diarrhea [4]. Metronidazole and vancomycin are the drugs of choice for the treatment of CDI; they are associated with a high incidence of relapse [8]. Recurrent or persistent CDI have been linked to the ability to produce biofilms [11]. Given the poor efficacy of standard treatment for frequent recurrences of CDIs, researchers have been actively searching treatment alternatives for several decades
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