Related Experiment Video

Updated: Aug 25, 2026

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes
07:44

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes

Published on: February 14, 2025

Training a phage to expand its host range: directed evolution against Staphylococcus aureus from diabetic foot

Lucile Plumet1, Chloé Magnan1, Madjid Morsli1

  • 1VBIC, INSERM U1047, Department of Microbiology and Hospital Hygiene, University of Montpellier, CHU Nîmes, Nîmes, France.

Antimicrobial Agents and Chemotherapy
|August 24, 2026
PubMed

Insights

Phage therapy using trained SAVM02-P20 shows promise for treating diabetic foot infections (DFIs) caused by Staphylococcus aureus. However, in vitro training did not fully translate to in vivo efficacy, indicating challenges for chronic infection treatment.

Area of Science:

  • Microbiology
  • Virology
  • Infectious Diseases

Background:

  • Diabetic foot infections (DFIs) are a significant complication of diabetes, often caused by multidrug-resistant Staphylococcus aureus.
  • Conventional antibiotic treatments for DFIs face challenges due to bacterial resistance and therapeutic complexity.
  • Bacteriophage (phage) therapy presents a potential alternative, but limited host range of individual phages restricts clinical application.

Purpose of the Study:

  • To enhance the host range and efficacy of the staphylococcal phage SAVM02 against Staphylococcus aureus strains relevant to DFIs through directed evolution.
  • To investigate the mechanisms underlying phage adaptation and host-range expansion.
  • To evaluate the in vitro and in vivo therapeutic potential of the trained phage pool (SAVM02-P20) for DFI treatment.

Main Methods:

  • Directed evolution of the staphylococcal phage SAVM02 through 20 iterative passages on a mixed panel of susceptible and non-susceptible S. aureus strains.
  • Assessment of the trained phage pool's (SAVM02-P20) infectivity against a diverse collection of S. aureus isolates and related staphylococci.
  • Genomic and phylogenetic analyses to identify adaptive changes in the evolved phage.
  • In vivo efficacy testing using a zebrafish embryo model to evaluate therapeutic benefits against susceptible and poorly permissive S. aureus strains.

Main Results:

  • The trained phage pool (SAVM02-P20) exhibited significantly enhanced activity, infecting approximately 77% of tested S. aureus isolates and showing partial cross-species activity against coagulase-negative staphylococci.
  • Improved infectivity was attributed to increased replication efficiency rather than enhanced adsorption.
  • Genomic analysis revealed recurrent adaptive changes and host-range expansion within genetically related lineages.
  • In vivo studies confirmed therapeutic efficacy against a susceptible strain but showed no survival benefit against an initially poorly permissive isolate.

Conclusions:

  • Phage training via directed evolution can broaden the host range and improve the lytic activity of bacteriophages against clinically relevant bacteria like S. aureus.
  • The study highlights a discrepancy between in vitro phage adaptation and in vivo therapeutic efficacy, particularly for chronic infections.
  • Integrating evolutionary approaches with physiologically relevant models is crucial for optimizing phage therapy for complex infections such as DFIs.
Keywords:
Staphylococcus aureusbacteriophagesdiabetic foot infectionsphage trainingzebrafish model

More Related Videos

A Practical Guide to Phage- and Robotics-Assisted Near-Continuous Evolution05:08

A Practical Guide to Phage- and Robotics-Assisted Near-Continuous Evolution

Published on: January 12, 2024

Related Concept Videos

Lytic Cycle of Bacteriophages01:30

Lytic Cycle of Bacteriophages

Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the lytic replication...
DNA Bacteriophages01:26

DNA Bacteriophages

Bacteriophages, or phages, are viruses that specifically infect bacteria, utilizing their genetic material to hijack host cellular machinery for replication. DNA bacteriophages employ single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) genomes. These phages exhibit diverse replication strategies and host interactions, influencing their ecological roles and applications in biotechnology and medicine.ssDNA BacteriophagesssDNA phages, with their small genomes, utilize unique strategies to...
Evolution of New Traits in Microbes01:24

Evolution of New Traits in Microbes

Microorganisms evolve rapidly due to their large population sizes and short generation times, often exhibiting measurable changes within days under laboratory conditions. Natural selection acts on standing genetic variation, enabling the retention and amplification of beneficial traits that confer fitness advantages in changing environments.Adaptive Pigment Regulation in RhodobacterIn Rhodobacter, a genus of purple non-sulfur bacteria, light-harvesting pigments such as bacteriochlorophyll and...
Bacteriophages of the Human Virome01:23

Bacteriophages of the Human Virome

Bacteriophages are found throughout the human body. They may even outnumber eukaryotic viruses, forming an important and dynamic component of the human virome. Indeed, phages represent the most abundant viral entities, with densities in the gut reaching up to 10⁹ particles per gram of fecal matter, and many belonging to orders such as Caudovirales and Microviridae, while a substantial proportion remains unclassified as viral “dark matter.”Lysogeny and Genetic ExchangeIn the gut, bacteriophages...
Lysogenic Cycle of Bacteriophages00:43

Lysogenic Cycle of Bacteriophages

In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
Transduction01:16

Transduction

Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome are...