JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range.

Tingting Feng,Ke Dong,Zelin Cui,Xiaokui Guo,Belinda Loh,Sebastian Leptihn,Yan Zhang,Mingyue Li,Melanie I Stefan

doi:10.3389/fmicb.2021.602902

Abstract

Phage therapy represents a possible treatment option to cure infections caused by multidrug-resistant bacteria, including methicillin and vancomycin-resistant Staphylococcus aureus, to which most antibiotics have become ineffective. In the present study, we report the isolation and complete characterization of a novel phage named JD219 exhibiting a broad host range able to infect 61 of 138 clinical strains of S. aureus tested, which included MRSA strains as well. The phage JD419 exhibits a unique morphology with an elongated capsid and a flexible tail. To evaluate the potential of JD419 to be used as a therapeutic phage, we tested the ability of the phage particles to remain infectious after treatment exceeding physiological pH or temperature. The activity was retained at pH values of 6.0–8.0 and below 50°C. As phages can contain virulence genes, JD419’s complete genome was sequenced. The 45509 bp genome is predicted to contain 65 ORFs, none of which show homology to any known virulence or antibiotic resistance genes. Genome analysis indicates that JD419 is a temperate phage, despite observing rapid replication and lysis of host strains. Following the recent advances in synthetic biology, JD419 can be modified by gene engineering to remove prophage-related genes, preventing potential lysogeny, in order to be deployed as a therapeutic phage.

Highlights

Antimicrobial resistance (AMR) presents a significant threat to humankind
Strains were identified by the VITEK 2 Compact (Biomerieux); 76 strains were MSSA, 59 strains were MRSA (Methicillin-resistant Staphylococcus aureus), which were tested for resistance to cefoxitin; detailed information can be found in the Supplementary Material
Phage JD419 Has a Flexible Tail Attached to a Prolate Capsid

Summary

Introduction

Antimicrobial resistance (AMR) presents a significant threat to humankind. A study estimates that in 2050 about 10 million people will die annually from untreatable bacterial infections if alternatives and novel antibiotics are not available (O’Neill, 2014). -called antimicrobial stewardship programs aim to optimize antibiotic use to decrease the emergence and spread of infections caused by multidrugresistant organisms (Manohar et al, 2020b). Due to this and the lack of financial incentives for the pharmaceutical industry to develop new antibiotics, alternative treatment strategies are urgently needed. One such strategy is the deployment of bacterial viruses that infect and kill bacteria, known as phage therapy (Manohar et al, 2020a). Phage therapy shows promising potential for treating methicillinas well as vancomycin-resistant S. aureus (Moellering, 2012; Limbago et al, 2014) as phages can infect multidrug-resistant bacteria (Lobocka et al, 2012; Kazmierczak et al, 2014)

Methods

Results

Conclusion