Parallel Evolution of Host-Attachment Proteins in Phage PP01 Populations Adapting to Escherichia coli O157:H7
| Autor: | Elizabeth Williams, Chidiebere Akusobi, Benjamin K Chan, Paul E. Turner, John E. Wertz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
antibiotic resistance phage therapy Phage therapy medicine.medical_treatment Pharmaceutical Science Virulence lcsh:Medicine lcsh:RS1-441 medicine.disease_cause Bacteriophage lcsh:Pharmacy and materia medica 03 medical and health sciences bacteriophage Molecular evolution Drug Discovery medicine Escherichia coli experimental evolution Gene Genetics Experimental evolution biology molecular evolution Point mutation lcsh:R biology.organism_classification 030104 developmental biology Molecular Medicine |
| Zdroj: | Pharmaceuticals Volume 11 Issue 2 Pharmaceuticals, Vol 11, Iss 2, p 60 (2018) |
| ISSN: | 1424-8247 |
| DOI: | 10.3390/ph11020060 |
| Popis: | The emergence of antibiotic resistance has sparked interest in phage therapy, which uses virulent phages as antibacterial agents. Bacteriophage PP01 has been studied for potential bio-control of Escherichia coli O157:H7, its natural host, but in the laboratory, PP01 can be inefficient at killing this bacterium. Thus, the goal of this study was to improve the therapeutic potential of PP01 through short-term experimental evolution. Four replicate populations of PP01 were serially passaged 21 times on non-evolving E. coli O157:H7 with the prediction that the evolved phage populations would adsorb faster and more efficiently kill the host bacteria. Dead-cell adsorption assays and in vitro killing assays confirmed that evolved viruses improved their adsorption ability on E. coli O157:H7, and adapted to kill host bacteria faster than the wildtype ancestor. Sequencing of candidate tail-fiber genes revealed that the phage populations evolved in parallel the lineages shared two point mutations in gp38 that encodes a host recognition protein, and surprisingly shared a ~600 bp deletion in gp37 that encodes the distal tail fibers. In contrast, no mutations were observed in the gp12 gene encoding PP01&rsquo s short tail fibers. We discuss the functional role of the observed mutations, including the possible adaptive role of the evolved deletions. This study demonstrates how experimental evolution can be used to select for viral traits that improve phage attack of an important bacterial pathogen, and that the molecular targets of selection include loci contributing to cell attachment and phage virulence. |
| Databáze: | OpenAIRE |
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