Transcriptional Analysis of the Effects of Gambogic Acid and Neogambogic Acid on Methicillin-Resistant Staphylococcus aureus.

Xin Hua,Yue Jia,Siguo Liu,Zhimin Dong,Qin Yang,Wanjiang Zhang

doi:10.3389/fphar.2019.00986

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major threat to human health, as this bacterium has developed resistance to a variety of conventional antibiotics. This is especially true of MRSA biofilms, which not only exhibit enhanced pathogenicity but also are resistant to most antibiotics. In this work, we demonstrated that two natural products with antitumor activity, namely, gambogic acid (GA) and neogambogic acid (NGA), have significant inhibitory activity toward MRSA. GA and NGA can not only effectively inhibit planktonic MRSA strains in vivo and in vitro, but also have strong inhibitory effects on MRSA biofilms formation. By transcriptome sequencing, Q-RT-PCR and PRM, we found that GA and NGA could reduce the expression of S. aureus virulence factors by inhibiting the saeRS two-component, thus achieving inhibition of MRSA. We found that GA and NGA had anti-MRSA activity in vivo and in vitro and identified saeRS to be the target, indicating that saeRS inhibitors may be used to treat biofilm-related infections.

Highlights

Methicillin-resistant Staphylococcus aureus (MRSA) can induce multiple human diseases, such as necrotic pneumonia, endocarditis, and septicemia (Tenover and Goering, 2009; Alam et al, 2015; David and Daum, 2017)
We reported for the first time that gambogic acid (GA) and neogambogic acid (NGA) have the activity of inhibiting MRSA biofilm formation, and revealed the new mechanism of the antimicrobial activity of GA and NGA
For MRSA inhibition, the Minimal inhibitory concentration (MIC) of oxacillin was 64 μg/mL, the MICs of GA and NGA remained between 0.5 μg/mL and 4 μg/mL

Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) can induce multiple human diseases, such as necrotic pneumonia, endocarditis, and septicemia (Tenover and Goering, 2009; Alam et al, 2015; David and Daum, 2017). Due to significant resistance of MRSA to a wide range of antibiotics, treatment tends to be ineffective, especially after biofilm formation, which limits the number of therapeutic options available (Pozzi et al, 2012; Ohadian Moghadam et al, 2014; Vazquez-Sanchez et al, 2018). Two Staphylococcus aureus saeRS Inhibitors for the medical field worldwide, and antibiotics remains the major method of treatment. The development of novel therapeutic agents and antibiotic substitutes with activity against highly pathogenic bacteria is urgently required

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Conclusion