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Molecular Basis for Lytic Bacteriophage Resistance in Enterococci
Breck A Duerkop1, Wenwen Huo2, Pooja Bhardwaj2
1Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Mbio
|September 1, 2016
Summary
Phage therapy faces challenges from bacteria developing resistance. Researchers identified a key protein in Enterococcus faecalis, PIPEF, involved in phage infection and resistance, offering insights for improved phage treatments.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- The rise of multidrug-resistant bacteria necessitates alternative treatments like phage therapy.
- Bacterial resistance to phages is a significant hurdle for effective phage therapy.
- Enterococcus faecalis is an opportunistic pathogen that can cause infections and is developing antibiotic resistance.
Purpose of the Study:
- To identify novel lytic phages targeting Enterococcus faecalis.
- To elucidate the molecular mechanisms of phage resistance in E. faecalis.
- To explore strategies for engineering phages to overcome bacterial resistance.
Main Methods:
- Isolation of lytic phages from municipal raw sewage.
- Identification and characterization of the phage infection protein PIPEF in E. faecalis.
- Utilizing a gnotobiotic mouse model to study in vivo phage predation and resistance development.
Main Results:
- Novel lytic phages targeting E. faecalis were identified.
- A conserved integral membrane protein, PIPEF, was found essential for phage infection and harbors a hypervariable region determining phage tropism.
- In vivo studies demonstrated temporary reduction of E. faecalis by phages, with resistance emerging through mutations in PIPEF.
Conclusions:
- The study defines the molecular basis of an evolutionary arms race between E. faecalis and lytic phages.
- Understanding PIPEF's role provides a basis for engineering E. faecalis phages with altered host specificity and resistance-evading capabilities.
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