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Updated: Sep 7, 2025
Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
Antibiotic Exposure Leads to Reduced Phage Susceptibility in Vancomycin Intermediate Staphylococcus aureus (VISA)
Shawna McCallin1,2, Carmen Menzi1, Swenja Lassen2
1Department of Fundamental Microbiology, University of Lausannegrid.9851.5, Lausanne, Switzerland.
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.
Insights
Vancomycin-intermediate Staphylococcus aureus (VISA) infections may develop phage resistance after vancomycin exposure. This resistance interferes with phage DNA replication, impacting phage therapy effectiveness against these difficult-to-treat infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacteriophage Therapy
Background:
- Antimicrobial resistance necessitates alternative treatments like phage therapy.
- Vancomycin-intermediate Staphylococcus aureus (VISA) presents a growing clinical challenge.
- Phage therapy is being explored for VISA infections.
Purpose of the Study:
- To investigate potential cross-resistance between vancomycin and phage in VISA strains.
- To understand the mechanism of phage resistance induced by vancomycin exposure.
Main Methods:
- Comparative analysis of genetically similar VISA strains with varying vancomycin susceptibility.
- Serial passaging experiments with vancomycin.
- Adsorption assays, lysostaphin sensitivity assays, electron microscopy, and quantitative PCR (qPCR) to analyze phage infection stages.
Main Results:
- VISA strains with intermediate vancomycin resistance showed reduced sensitivity to phage.
- Serial vancomycin passaging induced both decreased vancomycin susceptibility and phage sensitivity.
- Phage infection was halted post-DNA ejection but prior to DNA replication in vancomycin-exposed strains.
Conclusions:
- Vancomycin exposure can induce cross-resistance to phage in VISA strains.
- This resistance mechanism impedes phage DNA replication, potentially limiting phage therapy efficacy.
- Understanding antibiotic-phage resistance interactions is crucial for developing effective therapeutic strategies.
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