Identification of a Human Anti-Alpha-Toxin Monoclonal Antibody Against Staphylococcus aureus Infection.

Fangjie Liu,Yaping Gao,Jingjing Li,Yuanfang Ma,Beifen Shen,Zhangchun Guan,Chenghua Liu,Guang Yang,Jiannan Feng,Yu Liu

doi:10.3389/fmicb.2021.692279

Abstract

Staphylococcus aureus is a major pathogenic bacterium that causes a variety of clinical infections. The emergence of multi-drug resistant mechanisms requires novel strategies to mitigate S. aureus infection. Alpha-hemolysin (Hla) is a key virulence factor that is believed to play a significant role in the pathogenesis of S. aureus infections. In this study, we screened a naïve human Fab library for identification of monoclonal antibodies targeting Hla by phage display technology. We found that the monoclonal antibody YG1 blocked the Hla-mediated lysis of rabbit red blood cells and inhibited Hla binding to A549 cells in a concentration-dependent manner. YG1 also provided protection against acute peritoneal infection, bacteremia, and pneumonia in murine models. We further characterized its epitope using different Hla variants and found that the amino acids N209 and F210 of Hla were functionally and structurally important for YG1 binding. Overall, these results indicated that targeting Hla with YG1 could serve as a promising protective strategy against S. aureus infection.

Highlights

Staphylococcus aureus is an important pathogen that causes a diverse array of illnesses, from minor skin infections to life-threatening diseases, such as sepsis and pneumonia (Beceiro et al, 2013; Thammavongsa et al, 2013; Monaco et al, 2017; Lakhundi and Zhang, 2018)
We found that Hla could lyse rabbit red blood cells (RBCs) and bind to A549 cells (Figures 1A,B)
Infection caused by multidrug-resistant S. aureus has become a serious threat to public health worldwide

Summary

Introduction

Staphylococcus aureus is an important pathogen that causes a diverse array of illnesses, from minor skin infections to life-threatening diseases, such as sepsis and pneumonia (Beceiro et al, 2013; Thammavongsa et al, 2013; Monaco et al, 2017; Lakhundi and Zhang, 2018). Antibiotics are the standard treatment for S. aureus infections; due to the rapid development of antibiotic-resistant S. aureus, treatment is complicated (Gordon and Lowy, 2008; Harris et al, 2010; Espadinha et al, 2013). In order to avoid the spread of antibiotics resistance, researchers have focused on developing novel strategies to mitigate S. aureus infection (Tkaczyk et al, 2012; Oganesyan et al, 2014; Lehar et al, 2015; Liu et al, 2015). Extracellular toxins play a significant role in the pathogenesis of S. aureus infection. Inhibition of toxins is thought to provide less selective pressure for the development of resistance compared to killing bacteria or preventing their growth.

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