Abstract
BackgroundStaphylococcal aureus (S. aureus) has become the leading causative pathogen of Prosthetic Joint Infection (PJI), which is the most devastating complication after arthroplasty surgeries. Due to the biofilm formation ability and emergence of multiple-drugs resistance strains of S. aureus, it has become an urgency to find new anti-staphylococcal agents to establish effective prophylaxis and treatment strategy for PJI. Extracted from a traditional Chinese herb, berberine is proved active in inhibiting S. aureus, while whether it exerts the same effect on PJI-related S. aureus remains unknown. This study aims to investigate the antimicrobial activity of berbrine against clinical derived PJI-related S. aureus and whether its inhibiting efficacy is associated with subtypes of S. aureus.MethodsEighteen PJI-associated S. aureus were collected and their Multi-locus Sequence Types (MLST) and susceptibility to berberine both in planktonic and biofilm form were investigated. Additionally, one S. aureus strain (ST1792) was selected from the group and its transcriptomic profiling in berberine incubation was performed. The statistical analyses were conducted using Student’s t-test with SPSS 24.0(SPSS, IBM, USA). The data were expressed as the means ± standard deviation. Values of p < 0.05 were considered statistically significant.ResultsIt was found out that the Minimum Inhibitory Concentration values of PJI-related S. aureus varied in a broad range (from 64 to 512 μg/ml) among different MLST subtypes and the bacteria were able to regain growth after 24 h in berberine of MIC value or higher concentrations. In addition, sub-inhibitory concentrations of berberine surprisingly enhanced biofilm formation in some S. aureus strains.ConclusionTraditional medicine is utilised by a large number of individuals, which provides abundant resources for modern medical science. In our study, berberine was found bactericidal against PJI related S. aureus, however, its antibacterial property was impacted by the MLST subtypes of the bacteria, both in planktonic and biofilm growth forms.
Highlights
Staphylococcal aureus (S. aureus) has become the leading causative pathogen of Prosthetic Joint Infection (PJI), which is the most devastating complication after arthroplasty surgeries
The Minimum Inhibitory Concentration (MIC) values to berberine of 18 S. aureus isolates varied among different Multi-locus Sequence Types (MLST) types The MLST test showed that 18 PJI-related S. aureus isolates fell into eleven sub-types, with 1 each into ST15, ST17, ST188, ST39, ST1792, ST88, ST8, 2 into ST1281 and 3 into ST630, ST7, ST239 (Table 3), respectively
Berberine exerted excellent inhibiting effect on PJIrelated S. aureus strains in planktonic form Within 2 h of incubation, no significant growth of all tested S. aureus was detected (Fig. 1a and b)
Summary
Staphylococcal aureus (S. aureus) has become the leading causative pathogen of Prosthetic Joint Infection (PJI), which is the most devastating complication after arthroplasty surgeries. Extracted from a traditional Chinese herb, berberine is proved active in inhibiting S. aureus, while whether it exerts the same effect on PJI-related S. aureus remains unknown. This study aims to investigate the antimicrobial activity of berbrine against clinical derived PJI-related S. aureus and whether its inhibiting efficacy is associated with subtypes of S. aureus. The MLST types of the clinical S. aureus were not determined while different subtypes of S. aureus could have vastly different sensitivity to the same antimicrobial agents. These disadvantages may hinder the way of applying berberine into clinical PJI control. In this study, we collected eighteen PJI-associated clinical S. aureus strains, determined their MLST types and tested the inhibitory effect of berberine against S. aureus in planktonic and biofilm status. Bioinformatics analysis including DEGs (Differentially Expressed Genes) selection, GO (Gene Ontology Consortium) functional enrichment and pathway significance enrichment were conducted
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