Suppressing Alpha-Hemolysin as Potential Target to Screen of Flavonoids to Combat Bacterial Coinfection.

Shangwen He,Xiaoye Liu,Bingbing Liang,Xiaohan Yu,Dawei Guo,Qian Deng,Feike Yu,Hong Dong

doi:10.3390/molecules26247577

Abstract

The rapid emergence of bacterial coinfection caused by cytosolic bacteria has become a huge threat to public health worldwide. Past efforts have been devoted to discover the broad-spectrum antibiotics, while the emergence of antibiotic resistance encourages the development of antibacterial agents. In essence, bacterial virulence is a factor in antibiotic tolerance. However, the discovery and development of new antibacterial drugs and special antitoxin drugs is much more difficult in the antibiotic resistance era. Herein, we hypothesize that antitoxin hemolytic activity can serve as a screening principle to select antibacterial drugs to combat coinfection from natural products. Being the most abundant natural drug of plant origins, flavonoids were selected to assess the ability of antibacterial coinfections in this paper. Firstly, we note that four flavonoids, namely, baicalin, catechin, kaempferol, and quercetin, have previously exhibited antibacterial abilities. Then, we found that baicalin, kaempferol, and quercetin have better inhibitions of hemolytic activity of Hla than catechin. In addition, kaempferol and quercetin, have therapeutic effectivity for the coinfections of Staphylococcus aureus and Pseudomonas aeruginosa in vitro and in vivo. Finally, our results indicated that kaempferol and quercetin therapied the bacterial coinfection by inhibiting S. aureus α-hemolysin (Hla) and reduced the host inflammatory response. These results suggest that antitoxins may play a promising role as a potential target for screening flavonoids to combat bacterial coinfection.

Highlights

The dissemination of bacterial infections accelerates the emergence of antibiotic tolerance [1,2,3]
The antihemolytic activity of flavonoids against S. aureus Hla were detected (Figure 2A); results showed that catechin did not have any antihemolytic activity under the concentrations of 8–128 μg/mL, whereas baicalin, quercetin, and kaempferol could inhibit the hemolysis of Hla (Figure 2B,C)
Reports show that antibacterial activity of catechins isolated from cashew nut shells and found that catechins have the potential to resist methicillin-resistant Staphylococcus aureus (MRSA), which can increase the production of reactive oxygen species and reduce the oxidative stress of antioxidant enzymes [31]

Summary

Introduction

The dissemination of bacterial infections accelerates the emergence of antibiotic tolerance [1,2,3]. The respiratory coinfections correlated with multiple bacterial pathogens are worse than the one with a single kind of bacterium in clinic [6,7,8]. The increasing emergence of bacterial coinfections is paralyzing our public health systems worldwide [9,10]. Infections caused by mixed bacteria with unknown mechanisms are diminishing the discovery and development of new antibacterial drugs. Efficacious and novel antimicrobial agents remain the most effective strategy for the treatment of bacterial coinfections. There are urgent and unmet demands to identify novel or potential targets and to develop new antibacterial drugs with distinct modes of action to prevent such coinfections

Objectives

Methods

Results

Conclusion