Synergistic Antibacterial Activity with Conventional Antibiotics and Mechanism of Action of Shikonin against Methicillin-Resistant Staphylococcus aureus

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a troublesome pathogen that poses a global threat to public health. Shikonin (SKN) isolated from Lithospermum erythrorhizon (L. erythrorhizon) possesses a variety of biological activities. This study aims to explore the effect of the combined application of SKN and traditional antibiotics on the vitality of MRSA and the inherent antibacterial mechanism of SKN. The synergies between SKN and antibiotics against MRSA and its clinical strain have been demonstrated by the checkerboard assay and the time-kill assay. The effect of SKN on disrupting the integrity and permeability of bacterial cell membranes was verified by a nucleotide and protein leakage assay and a bacteriolysis assay. As determined by crystal violet staining, SKN inhibited the biofilm formation of clinical MRSA strains. The results of Western blot and qRT-PCR showed that SKN could inhibit the expression of proteins and genes related to drug resistance and S. aureus exotoxins. SKN inhibited the ability of RAW264.7 cells to release the pro-inflammatory cytokines TNF-α and IL-6, as measured by ELISA. Our findings suggest that SKN has the potential to be developed as a promising alternative for the treatment of MRSA infections.

Endophytes: a uniquely tailored source of potential antibiotic adjuvants

“…Both a standalone and an antibiotic adjuvant Mishra et al 2020 ); Viszwapriya et al ( 2016 ) Molecules showing aminoglycosides synergism 16 Phenol, 2,4-bis(1,1-dimethylethyl) Seaweed Gracilaria gracilis Vibrio alginolyticus G16 Reduction of virulence factors and EPS up to 84% Reduce biofilm formation in Serratia marcescens , revealed a synergistic effect with gentamicin Padmavathi et al ( 2014 ); Chen et al (2019) 17 Venturicidin A Scindapsus hederaceus, Shorea ovalis and Zingiber71 spectabile Streptomyces SUK 10 Uncoupling of ATP synthesis Gentamycin potentiation Yarlagadda et al ( 2020 ) 18 Shikonin Roots of Lithospermum officinale Fusarium tricinctum Inhibit the protein expression related to drug resistance and S. aureus exotoxins Reduced the MIC of streptomycin by up to 16-fold. Active against S. aureus RN4220 with MIC of 16 mg/L Mone et al ( 2021 ); Mollaei et al ( 2019 ); Li et al ( 2022 ) Molecules showing cephalosporins synergism 19 Chitosan Several plant sources Aspergillus flavus Reduction in lasR and rhlR genes expression Showed synergism with ceftazidime with a reduction in MIC from 128 to 64 μg/ml. Reduced biofilm formation of P. aeruginosa Muslim et al ( 2018 ) QS and biofilm inhibitors (unidentified synergism) 20 (5S,6S)-6-((3’S,4’S,Z)-3’,4’-Dihydroxypent-1-en-1-yl)-5-hydroxy-5,6-dihydro-2H-pyran-2-one Tropical palm Astrocaryum sciophilum Lasiodiplodia venezuelensis …”

Endophytes: a uniquely tailored source of antibiotic adjuvants

“…For instance, phomopsolides from the endophytic Penicillium sp. displayed feeding deterrent effects for Scolytid beetles [43,44].…”

The anti-leukemia activity and mechanisms of shikonin: a mini review

“…The synergistic effects between chemotherapeutic agents, antibiotics and SHK were widely studied (Wang et al, 2019;Li et al, 2022;Tabari et al, 2022). Due to the different mechanisms of inhibiting receptor tyrosine kinase, SHK derivative betahydroxyisovalerylshikonin showed synergistic effect with imatinib on the induction of apoptosis in K562 cells (Nakaya and Miyasaka, 2003).…”