Abstract
Antimicrobial resistance has become a serious threat to human and animal health, and vancomycin-resistant Enterococcus has become an important nosocomial infection pathogen, causing thousands of deaths each year. In this study, after screening a variety of natural products, we found that cajanin stilbene acid (CSA) had significant inhibitory effect on sensitive and vancomycin-resistant Enterococcus (VRE) in vitro. And we also confirmed that CSA had significant anti-VRE infection ability in vivo. Subsequently, we studied the antibacterial mechanism of CSA through proteomics experiments, and the results showed that CSA killed Enterococcus by inhibiting the phosphotransferase system of Enterococcus, thus hinders the normal growth and metabolic functions of bacteria. The results of this study provided evidence for the in-depth study on the mechanism of the antibacterial action of CSA and also provided a candidate for the development of anti-VRE drugs.
Highlights
Enterococcus is one of the most common conditionally pathogenic gram-positive bacteria, when the human body immunity is low or defects, Enterococcus will lead to multiple organ infection, such as urinary tract infection, soft tissue infection, it cause severe infection such as bacteremia and endocarditis (Arias and Murray, 2012; Van Harten et al, 2017)
In 2017, according to “Antibiotic resistance threats in the United States”, about 54,500 people were infected with vancomycin-resistant Enterococcus (VRE) and 5,400 people died of VRE infection in the United States
After 2 h at 37°C and 200 rpm, the strain was treated with 10 mg/ml (5 × minimum inhibitory concentration (MIC)) vancomycin or cajanin stilbene acid (CSA) for 24 h, colony-forming unit (CFU) was calculated and the experiment was repeated for three times
Summary
Enterococcus is one of the most common conditionally pathogenic gram-positive bacteria, when the human body immunity is low or defects, Enterococcus will lead to multiple organ infection, such as urinary tract infection, soft tissue infection, it cause severe infection such as bacteremia and endocarditis (Arias and Murray, 2012; Van Harten et al, 2017). Vancomycin, a glycopeptide antibiotic, is used as a “last line of defense” against severe enterococcal and other Gram-positive bacterial infections which do not respond to other antibiotics (Park and Liu, 2012). It is of great significance to develop new anti-VRE drug candidates. Plants contain a considerable number of natural products with medicinal activity, which have been paid more and more attention in anti-infection, and are a promising source of new chemical. Natural products from a variety of plant sources have been assigned with significant antibacterial activity (Silva et al, 2016; Salam and Quave, 2018). This study elucidated the unique antibacterial mechanism of CSA and provided evidence for the development of VRE antibacterial drug candidates
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