Phage–Antibiotic Combination Therapy

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Bacterial Viruses".

Deadline for manuscript submissions: 20 January 2026 | Viewed by 988

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Guest Editor
Center for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M AgriLife Research, Texas A&M University, College Station, TX 77843, USA
Interests: phage biology; phage lysis system; phage therapy
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Special Issue Information

Dear Colleagues,

Antibiotic resistance is evolving into a significant health concern worldwide. The utilization of bacteriophages, viruses that target bacteria, to address infections caused by bacteria is garnering global interest. Phage therapy is in its developing phase and demonstrating efficacy as a tailored treatment. Phage treatment interventions in individuals with antibiotic-resistant bacterial infections are yielding favorable results. However, phage therapy presents several hurdles, including the emergence of phage resistance, the development of anti-phage antibody responses, and difficulties in addressing biofilms, among others. To address these issues associated with phage (mono) therapy, phage–antibiotic combination therapy can be employed to augment bacterial eradication, diminish the likelihood of resistance development, and ultimately enhance therapeutic outcomes.

This Special Issue focuses on recent findings regarding the combination of phage–antibiotic therapies for the treatment of bacterial infections. Phage–antibiotic synergy occurs when sublethal doses of specific antibiotics augment the binding efficacy of phages, resulting in enhanced bacterial eradication. Moreover, antibiotic-resistant bacteria may regain sensitivity to specific antibiotics in the presence of phage as a result of stress. Complex infections, such as biofilm and multi-bacterial infections, are effectively managed using phage–antibiotic combination therapy. There are unexplored areas to investigate, including therapeutic techniques and pre-phage and post-phage administration. This Special Issue solicits research articles on phage biology and characterization, encompassing phage–antibiotic studies as well as in vitro and in vivo studies to enhance our comprehension of phage–antibiotic combination therapy.

Dr. Prasanth Manohar
Guest Editor

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Keywords

  • bacteriophage
  • antibiotics
  • phage therapy
  • phage–antibiotic synergy
  • combination therapy
  • in vitro study
  • sub-lethal dose
  • emerging alternative
  • bacteria-killing

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Published Papers (1 paper)

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Research

11 pages, 1161 KiB  
Article
In Vivo Emergence of Podovirus Resistance via tarS Mutation During Phage-Antibiotic Treatment of Experimental MSSA Endocarditis
by Jérémy Cherbuin, Jonathan Save, Emma Osswald and Grégory Resch
Viruses 2025, 17(8), 1039; https://doi.org/10.3390/v17081039 - 25 Jul 2025
Viewed by 361
Abstract
Phage therapy shows promise as an adjunct to antibiotics for treating Staphylococcus aureus infections. We previously reported a combined flucloxacillin/two-phage cocktail treatment selected for resistance to podovirus phage 66 in a rodent model of methicillin-susceptible S. aureus (MSSA) endocarditis. Here we show that [...] Read more.
Phage therapy shows promise as an adjunct to antibiotics for treating Staphylococcus aureus infections. We previously reported a combined flucloxacillin/two-phage cocktail treatment selected for resistance to podovirus phage 66 in a rodent model of methicillin-susceptible S. aureus (MSSA) endocarditis. Here we show that resistant clones harbor mutations in tarS, which encodes a glycosyltransferase essential for β-GlcNAcylation of wall teichoic acid (WTA). This WTA modification has been described in vitro as critical for podoviruses adsorption. Transcriptomics confirmed continued tarS expression in resistant clones, supporting a loss-of-function mechanism. Accordingly, phage 66 binding and killing were restored by WT tarS complementation. In addition, we investigated the counterintuitive innate susceptibility to phage 66 of the tarM + Laus102 strain used in the endocarditis model. We show that it likely results from a significant lower tarM expression, in contrast to the innate resistant strain RN4220. Our findings demonstrate that tarS-mediated WTA β-GlcNAcylation is critical for podovirus infection also in vivo and identify tarM transcriptional defect as a new mechanism of podoviruses susceptibility in S. aureus. Moreover, and since tarS disruption has been previously shown to enhance β-lactam susceptibility, our results support the development of combined podovirus/antibiotic strategies for the management of MRSA infections. Full article
(This article belongs to the Special Issue Phage–Antibiotic Combination Therapy)
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