Phage Resistance – Escherichia coli
The emergence of multidrug-resistant bacterial pathogens has led to a need for new therapeutic options, and the use of bacteriophages, also known as phages, has become an interesting option.
However, there is concern that phage-resistant mutants could rapidly evolve, compromising the efficacy of phage therapy.
In a recent study, scientists investigated this potential problem using the strictly lytic Escherichia phage vB_EcoM-P10 and the avian pathogenic E. coli (APEC) strain AM621.
The results showed that phage-resistant mutants emerged rapidly during the experiment.
Further analysis of these mutant strains revealed 41 individual genetic alterations that likely contributed to resistance.
This finding underscores the importance of understanding phage-host interactions and resistance mechanisms to successfully exploit the efficacy of phage therapy against bacterial pathogens.
The authors Patricia E Sørensen, Sharmin Baig, Marc Stegger, Hanne Ingmer, An Garmyn, and Patrick Butaye published these findings in their article Spontaneous Phage Resistance in Avian Pathogenic Escherichia coli, dated 13 December 2021.
- Avian pathogenic Escherichia coli (APEC) is a bacterial pathogen that affects poultry worldwide.
- Bacteriophages (phages) are being investigated as a potential therapy for APEC, but there are concerns about the emergence of phage-resistant mutants.
- In this study, the strictly lytic Escherichia phage vB_EcoM-P10 rapidly selected for resistance in APEC ST95 O1 strain AM621.
- Whole-genome sequencing of 109 spontaneous phage-resistant mutant strains revealed 41 mutants with single nucleotide polymorphisms (SNPs) in their nuclear genome, for a total of 34 unique SNPs. Gene losses in 17 different genes were detected in 42 strains, including two hypothetical genes.
- The infecting phages were unable to overcome phage resistance in the host strains. However, initial infection was shown to be a high fitness effort for several mutant strains.
Avian pathogenic Escherichia coli (APEC) is one of the most important bacterial pathogens affecting poultry worldwide.
The emergence of multidrug-resistant pathogens has renewed the interest in the therapeutic use of bacteriophages (phages).
However, a major concern for the successful implementation of phage therapy is the emergence of phage-resistant mutants. The understanding of the phage-host interactions, as well as underlying mechanisms of resistance, have shown to be essential for the development of a successful phage therapy.
Here, we demonstrate that the strictly lytic Escherichia phage vB_EcoM-P10 rapidly selected for resistance in the APEC ST95 O1 strain AM621. Whole-genome sequence analysis of 109 spontaneous phage-resistant mutant strains revealed 41 mutants with single-nucleotide polymorphisms (SNPs) in their core genome. In 32 of these, a single SNP was detected while two SNPs were identified in a total of nine strains. In total, 34 unique SNPs were detected. In 42 strains, including 18 strains with SNP(s), gene losses spanning 17 different genes were detected.
Affected by genetic changes were genes known to be involved in phage resistance (outer membrane protein A, lipopolysaccharide-, O- antigen-, or cell wall-related genes) as well as genes not previously linked to phage resistance, including two hypothetical genes.
In several strains, we did not detect any genetic changes. Infecting phages were not able to overcome the phage resistance in host strains.
However, interestingly the initial infection was shown to have a great fitness cost for several mutant strains, with up to ∼65% decrease in overall growth.
In conclusion, this study provides valuable insights into the phage-host interaction and phage resistance in APEC. Although acquired resistance to phages is frequently observed in pathogenic E. coli, it may be associated with loss of fitness, which could be exploited in phage therapy.
Keywords: Eschericha coli; bacteriophage; phage resistance; phage therapy; phage-host interaction.
Copyright © 2021 Sørensen, Baig, Stegger, Ingmer, Garmyn and Butaye.
Spontaneous phage resistance in avian pathogenic Escherichia coli (APEC) is the ability of certain strains of APEC to naturally develop resistance to certain types of phages, or virus that infect bacteria.
This phenomenon can occur due to mutations in the bacteria’s genetic material that allow it to evade the phage’s attack. In some cases, this spontaneous phage resistance can be beneficial to the bacteria, as it allows it to survive and thrive in environments where phages are present.
However, it can also be detrimental to the host, as it may lead to the spread of antibiotic-resistant strains of APEC.
To address this issue, it is important to monitor and control the spread of antibiotic-resistant APEC through proper hygiene and infection control measures.