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Viruses
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Phage–Antibiotic Combination Therapy
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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: 31 May 2026 | Viewed by 3505

Special Issue Editor

Dr. Prasanth Manohar

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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 (2 papers)

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Research

18 pages, 2644 KB  
Article
Rational Design of a Potent Two-Phage Cocktail Against a Contemporary Acinetobacter baumannii Strain Recovered from a Burned Patient at the Lausanne University Hospital
by Hugues de Villiers de la Noue, Gwenaëlle Golliard, Xavier Vuattoux and Grégory Resch
Viruses 2025, 17(11), 1441; https://doi.org/10.3390/v17111441 - 29 Oct 2025
Viewed by 1093
Abstract
Acinetobacter baumannii is a critical public health threat, particularly with the rise in multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains that limit treatment options. Phage therapy, which uses bacteriophages to target bacteria, offers a promising alternative. We isolated an XDR strain (Ab125) from [...] Read more.
Acinetobacter baumannii is a critical public health threat, particularly with the rise in multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains that limit treatment options. Phage therapy, which uses bacteriophages to target bacteria, offers a promising alternative. We isolated an XDR strain (Ab125) from a burn wound infection and screened 34 phages, identifying vB_AbaM_3098 as the only effective candidate. However, resistance rapidly emerged, producing a derivative strain (Ab139). Interestingly, Ab139, though resistant to vB_AbaM_3098, became susceptible to six previously inactive phages. While various potential determinants were identified through comparative genomics and proteomics, the mechanism causing phage resistance to vB_AbaM_3098 and simultaneous susceptibility to other phages remains to be elucidated. Among the six new candidates, vB_AbaM_3014 was the most promising. While each phage alone allowed bacterial regrowth, combining vB_AbaM_3098 and vB_AbaM_3014 completely suppressed Ab125 growth. In a Galleria mellonella infection model, this cocktail achieved 90% survival after five days compared to 0% in untreated controls. Notably, the cocktail combined one phage with modest activity and another inactive phage against the parental strain; together, they produced strong bactericidal effects. These findings highlight both the complexity of phage cocktail design and their promise as adjunct therapies against drug-resistant A. baumannii. Full article
(This article belongs to the Special Issue Phage–Antibiotic Combination Therapy)
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11 pages, 1161 KB  
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
Cited by 1 | Viewed by 1257
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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