Antibiotic Exposure Leads to Reduced Phage Susceptibility in Vancomycin Intermediate Staphylococcus aureus (VISA).

Content Provider	Europe PMC
Author	McCallin, Shawna Menzi, Carmen Lassen, Swenja Daraspe, Jean Oechslin, Frank Moreillon, Philippe
Copyright Year	2022
Abstract	In the time of antimicrobial resistance, phage therapy is frequently suggested as a possible solution for such difficult-to-treat infections. Vancomycin-intermediate Staphylococcus aureus (VISA) remains a relatively rare yet increasing occurrence in the clinic for which phage therapy may be an option. However, the data presented herein suggest a potential cross-resistance mechanism to phage following vancomycin exposure in VISA strains. When comparing genetically similar strains differing in their susceptibility to vancomycin, those with intermediate levels of vancomycin resistance displayed decreased sensitivity to phage in solid and liquid assays. Serial passaging with vancomycin induced both reduced vancomycin susceptibility and phage sensitivity. As a consequence, the process of phage infection was shown to be interrupted after DNA ejection from adsorbed phage but prior to phage DNA replication, as demonstrated through adsorption assays, lysostaphin sensitivity assays, electron microscopy, and quantitative PCR (qPCR). At a time when phage products are being used for experimental treatments and tested in clinical trials, it is important to understand possible interference between mechanisms underlying antibiotic and phage resistance in order to design effective therapeutic regimens.
Page Count	12
ISSN	00664804
Journal	Antimicrobial Agents and Chemotherapy
Volume Number	66
PubMed Central reference number	PMC9295574
Issue Number	7
PubMed reference number	35708333
e-ISSN	10986596
DOI	10.1128/aac.02247-21
Language	English
Publisher	American Society for Microbiology
Publisher Date	2022-06-16
Publisher Place	N.W., Washington, DC
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Copyright © 2022 McCallin et al.
Subject Keyword	bacteriophage phage therapy antibiotic resistance Staphylococcus aureus vancomycin VISA antimicrobial resistance staphylococcus
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)