Artesunate inhibits Staphylococcus aureus biofilm formation by reducing alpha-toxin synthesis
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ORIGINAL PAPER
Artesunate inhibits Staphylococcus aureus biofilm formation by reducing alpha‑toxin synthesis Yan Qian1 · Li Xia2 · Lai Wei1 · Di Li1 · Weiwei Jiang1 Received: 5 June 2020 / Revised: 13 September 2020 / Accepted: 1 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Staphylococcus aureus is one of the most common pathogens in bacterial biofilm infections. Antibiotic treatment for infection caused by S. aureus biofilms is challenging, and few effective strategies have been developed to combat these infections. The aim of this study was to investigate the effect and possible mechanisms of artesunate on the biofilm formation of S. aureus. Bacterial growth curves were determined by a microtiter plate. Biofilm formation was determined by the crystal violet staining method and confocal laser scanning microscopy. Bacterial adhesion was assayed by the colony-counting method. The expression of virulence and adhesion genes was determined by real-time PCR. The hemolytic activity and expression of ɑ-hemolysin were analyzed using rabbit erythrocytes and Western blotting. The results showed that artesunate could significantly inhibit the biofilm formation of S. aureus in a dose-dependent manner. Artesunate could also inhibit bacterial adhesion and the expression of hla, RNAIII and agrA as well as ɑ-hemolysin production. The effect of artesunate on adhesion genes (clfA, clfB, fnbA, fnbB) had strain specificity, but it did not affect the expression of ica genes. The results indicated that artesunate might inhibit ɑ-hemolysin synthesis by the agr system, which inhibits biofilm formation. Keywords Artesunate · Staphylococcus aureus · Biofilm · ɑ-hemolysin · Adhesion
Introduction Staphylococcus aureus is the most common gram-positive bacterium in clinical infections. In recent years, the emergence of multidrug-resistant bacteria has brought great difficulties to clinical diagnosis and treatment. Biofilm formation can enhance bacterial resistance to various antimicrobial drugs and enable bacteria to avoid human immune system attacks, which leads to chronic infection and recurrent infection (Otto 2018). In particular, patients with indwelling medical devices are at high risk of biofilm infections (Donlan 2001; San-Juan et al. 2017). Traditional antibiotics have Communicated by Erko stackebrandt. Yan Qian and Li Xia contributed equally to this work. * Weiwei Jiang [email protected] 1
Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, No. 76, Linjiang Road, Yuzhong District, Chongqing 400010, China
Department of Liver Disease, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China
2
limited the scavenging effects of bacterial biofilm infection. Despite the many reports identifying several compounds as antibiofilm agents in recent years (Balaban et al. 2007; Ahire and Dicks 2015; Carbone et al. 2018; Kumar et al. 2020), none of these compounds have reached clinical use. Therefore, there is an urgent need for the development of
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