Genetic Polymorphism Drives Susceptibility Between Bacteria and Bacteriophages.

Xiaoxu Zhang,Dongyan Xiong,Ping He,Hongping Wei,Hang Yang,Junping Yu

doi:10.3389/fmicb.2021.627897

Abstract

Phage therapy has attracted much attention for the treatment of antibiotic-resistant bacteria in recent years. However, it is common for bacteria to obtain resistance capability in short time after interaction with a lytic phage, as observed in phage therapy and co-culture of host and phage in a lab. In order to understand the mechanisms behind resistance, Staphylococcus aureus AB91118 and its lytic phage LQ7 were studied as a model system. A mutant strain named R1-3-1 resistant to the ancestral phage LQ7 was isolated, and then phages experimentally evolved from LQ7 were able to kill R1-3-1. Genomes of the two bacterial strains and the three phages (LQ7, ELQ7P-10, and ELQ7P-20) were analyzed based on deep sequencing data of NGS. Analyses showed that a few mutations could be identified in R1-3-1 and the evolved phages. Instead, in all the genomes of the bacteria and the phages, there exists genetic polymorphism of minor alleles, which distributes in many functional genes. Specifically, in the AB91118-LQ7 system it was found that the unique polymorphism sites in R1-3-1 associated to metabolic pathways could be inhibited by chloramphenicol (CHL). The resistant mutant R1-3-1 could become sensitive to the phage LQ7 in the presence of CHL. Combined use of CHL and the evolved phage from 20 cycles (ELQ7P-20) could produce the least resistance when killing the bacteria AB91118. The genetic polymorphism of minor alleles would be a new mechanism to drive the co-evolution between a phage and its host, which may enable the phage and the host get ready and fast response to the selective pressure from one to the other.

Highlights

With the emergence of antibiotic-resistant bacteria such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), the treatment of bacterial infections through antibiotics has become increasingly problematic (Sakoulas et al, 2005; Senok et al, 2019)
Like antibiotic resistance, the use of phages can lead to the emergence of phage-resistant strains, which would be a significant obstacle for phage therapy (Denes et al, 2015; El Haddad et al, 2018)
The results showed that besides mutations, a new mechanism, minor alleles in the genomes of the bacteria and the phages, would be important factors contributing to the resistance of the host to the phage and vice versa

Summary

Introduction

With the emergence of antibiotic-resistant bacteria such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), the treatment of bacterial infections through antibiotics has become increasingly problematic (Sakoulas et al, 2005; Senok et al, 2019). Phage therapy has attracted new interest for the treatment of antibiotic-resistant bacteria in recent years (Levin and Bull, 2004; Lyon, 2017). Lytic bacteriophages were used for phage therapy (Sulakvelidze et al, 2001). Phage therapy has been found to be effective for treatment of staphylococcal infections in animals Like antibiotic resistance, the use of phages can lead to the emergence of phage-resistant strains, which would be a significant obstacle for phage therapy (Denes et al, 2015; El Haddad et al, 2018). It is important to understand how bacteria and bacteriophage evolve in the presence of the other

Methods

Results

Conclusion