7 results on '"phage breeding"'
Search Results
2. Natural Bred ε2-Phages Have an Improved Host Range and Virulence against Uropathogenic Escherichia coli over Their Ancestor Phages
- Author
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Maria Loose, David Sáez Moreno, Michele Mutti, Eva Hitzenhammer, Zehra Visram, David Dippel, Susanne Schertler, Lenka Podpera Tišáková, Johannes Wittmann, Lorenzo Corsini, and Florian Wagenlehner
- Subjects
phage therapy ,phage breeding ,E. coli ,urinary tract infections ,phage training ,homologous recombination ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Alternative treatments for Escherichia coli infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 E. coli strains reflecting the diversity of strains found in UTI, including sequence type 131, 73 and 69. The plaquing host range (PHR) was between 13 and 63%. In contrast, the kinetic host range (KHR), describing the percentage of strains for which growth in suspension was suppressed for 24 h, was between 0% and 19%, substantially lower than the PHR. To improve the phage host range and their efficacy, we bred the phages by mixing and propagating cocktails on a subset of E. coli strains. The bred phages, which we termed evolution-squared ε2-phages, of a mixture of Myoviridae have KHRs up to 23% broader compared to their ancestors. Furthermore, using constant phage concentrations, Myoviridae ε2-phages suppressed the growth of higher bacterial inocula than their ancestors did. Thus, the ε2-phages were more virulent compared to their ancestors. Analysis of the genetic sequences of the ε2-phages with the broadest host range reveals that they are mosaic intercrossings of 2–3 ancestor phages. The recombination sites are distributed over the whole length of the genome. All ε2-phages are devoid of genes conferring lysogeny, antibiotic resistance, or virulence. Overall, this study shows that ε2-phages are remarkably more suitable than the wild-type phages for phage therapy.
- Published
- 2021
- Full Text
- View/download PDF
3. ε2-Phages Are Naturally Bred and Have a Vastly Improved Host Range in Staphylococcus aureus over Wild Type Phages
- Author
-
David Sáez Moreno, Zehra Visram, Michele Mutti, Marcela Restrepo-Córdoba, Susana Hartmann, Ana Isabel Kremers, Lenka Tišáková, Susanne Schertler, Johannes Wittmann, Benham Kalali, Stefan Monecke, Ralf Ehricht, Grégory Resch, and Lorenzo Corsini
- Subjects
phage therapy ,phage breeding ,phage training ,homologous recombination ,host range ,antimicrobial resistance ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for S. aureus infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 S. aureus strains (MRSA/MSSA) composed to reflect the prevalence of S. aureus clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%. We also measured what we called the kinetic host range (KHR), i.e., the percentage of strains for which growth in suspension was suppressed for 24 h. The KHR of the wild type phages ranged from 2% to 49%, substantially lower than the PHRs. To improve the KHR and other key pharmaceutical properties, we bred the phages by mixing and propagating cocktails on a subset of S. aureus strains. These bred phages, which we termed evolution-squared (ε2) phages, have broader KHRs up to 64% and increased virulence compared to the ancestors. The ε2-phages with the broadest KHR have genomes intercrossed from up to three different ancestors. We composed a cocktail of three ε2-phages with an overall KHR of 92% and PHR of 96% on 110 S. aureus strains and called it PM-399. PM-399 has a lower propensity to resistance formation than the standard of care antibiotics vancomycin, rifampicin, or their combination, and no resistance was observed in laboratory settings (detection limit: 1 cell in 1011). In summary, ε2-phages and, in particular PM-399, are promising candidates for an alternative treatment of S. aureus infections.
- Published
- 2021
- Full Text
- View/download PDF
4. Natural Bred ε2-Phages Have an Improved Host Range and Virulence against Uropathogenic Escherichia coli over Their Ancestor Phages
- Author
-
Johannes Wittmann, Maria Loose, Lorenzo Corsini, Michele Mutti, Lenka Tisakova, Florian M.E. Wagenlehner, David Dippel, Eva Hitzenhammer, Zehra Visram, Susanne Schertler, and David Sáez Moreno
- Subjects
Microbiology (medical) ,phage therapy ,Phage therapy ,medicine.medical_treatment ,viruses ,Virulence ,Myoviridae ,homologous recombination ,RM1-950 ,Biology ,medicine.disease_cause ,E. coli ,Biochemistry ,Microbiology ,Article ,Antibiotic resistance ,Lysogenic cycle ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,phage training ,Gene ,Escherichia coli ,biology.organism_classification ,phage breeding ,Infectious Diseases ,Lytic cycle ,Therapeutics. Pharmacology ,urinary tract infections - Abstract
Alternative treatments for Escherichia coli infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 E. coli strains reflecting the diversity of strains found in UTI, including sequence type 131, 73 and 69. The plaquing host range (PHR) was between 13 and 63%. In contrast, the kinetic host range (KHR), describing the percentage of strains for which growth in suspension was suppressed for 24 h, was between 0% and 19%, substantially lower than the PHR. To improve the phage host range and their efficacy, we bred the phages by mixing and propagating cocktails on a subset of E. coli strains. The bred phages, which we termed evolution-squared ε2-phages, of a mixture of Myoviridae have KHRs up to 23% broader compared to their ancestors. Furthermore, using constant phage concentrations, Myoviridae ε2-phages suppressed the growth of higher bacterial inocula than their ancestors did. Thus, the ε2-phages were more virulent compared to their ancestors. Analysis of the genetic sequences of the ε2-phages with the broadest host range reveals that they are mosaic intercrossings of 2–3 ancestor phages. The recombination sites are distributed over the whole length of the genome. All ε2-phages are devoid of genes conferring lysogeny, antibiotic resistance, or virulence. Overall, this study shows that ε2-phages are remarkably more suitable than the wild-type phages for phage therapy.
- Published
- 2021
- Full Text
- View/download PDF
5. ε
- Author
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Lorenzo Corsini, Susanne Schertler, Marcela Restrepo-Córdoba, Ana Isabel Kremers, Johannes Wittmann, Grégory Resch, Benham Kalali, Ralf Ehricht, Michele Mutti, Lenka Tisakova, David Sáez Moreno, Stefan Monecke, Susana Hartmann, and Zehra Visram
- Subjects
0301 basic medicine ,phage therapy ,Phage therapy ,medicine.drug_class ,medicine.medical_treatment ,030106 microbiology ,Antibiotics ,phage cocktail ,lcsh:Medicine ,lcsh:RS1-441 ,host range ,Pharmaceutical Science ,Virulence ,homologous recombination ,MRSA ,MSSA ,Biology ,medicine.disease_cause ,Article ,Microbiology ,lcsh:Pharmacy and materia medica ,03 medical and health sciences ,Antibiotic resistance ,Drug Discovery ,medicine ,antimicrobial resistance ,phage training ,lcsh:R ,Wild type ,S. aureus ,phage breeding ,030104 developmental biology ,Staphylococcus aureus ,Molecular Medicine ,Vancomycin ,Rifampicin ,medicine.drug - Abstract
Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for S. aureus infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 S. aureus strains (MRSA/MSSA) composed to reflect the prevalence of S. aureus clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%. We also measured what we called the kinetic host range (KHR), i.e., the percentage of strains for which growth in suspension was suppressed for 24 h. The KHR of the wild type phages ranged from 2% to 49%, substantially lower than the PHRs. To improve the KHR and other key pharmaceutical properties, we bred the phages by mixing and propagating cocktails on a subset of S. aureus strains. These bred phages, which we termed evolution-squared (ε 2 ) phages, have broader KHRs up to 64% and increased virulence compared to the ancestors. The ε 2 -phages with the broadest KHR have genomes intercrossed from up to three different ancestors. We composed a cocktail of three ε 2 -phages with an overall KHR of 92% and PHR of 96% on 110 S. aureus strains and called it PM-399. PM-399 has a lower propensity to resistance formation than the standard of care antibiotics vancomycin, rifampicin, or their combination, and no resistance was observed in laboratory settings (detection limit: 1 cell in 10 11 ). In summary, ε 2 -phages and, in particular PM-399, are promising candidates for an alternative treatment of S. aureus infections.
- Published
- 2021
6. Natural Bred ε 2 -Phages Have an Improved Host Range and Virulence against Uropathogenic Escherichia coli over Their Ancestor Phages.
- Author
-
Loose, Maria, Sáez Moreno, David, Mutti, Michele, Hitzenhammer, Eva, Visram, Zehra, Dippel, David, Schertler, Susanne, Tišáková, Lenka Podpera, Wittmann, Johannes, Corsini, Lorenzo, and Wagenlehner, Florian
- Subjects
ESCHERICHIA coli diseases ,ESCHERICHIA coli ,BACTERIOPHAGES ,URINARY tract infections ,DRUG resistance in bacteria - Abstract
Alternative treatments for Escherichia coli infections are urgently needed, and phage therapy is a promising option where antibiotics fail, especially for urinary tract infections (UTI). We used wastewater-isolated phages to test their lytic activity against a panel of 47 E. coli strains reflecting the diversity of strains found in UTI, including sequence type 131, 73 and 69. The plaquing host range (PHR) was between 13 and 63%. In contrast, the kinetic host range (KHR), describing the percentage of strains for which growth in suspension was suppressed for 24 h, was between 0% and 19%, substantially lower than the PHR. To improve the phage host range and their efficacy, we bred the phages by mixing and propagating cocktails on a subset of E. coli strains. The bred phages, which we termed evolution-squared ε
2 -phages, of a mixture of Myoviridae have KHRs up to 23% broader compared to their ancestors. Furthermore, using constant phage concentrations, Myoviridae ε2 -phages suppressed the growth of higher bacterial inocula than their ancestors did. Thus, the ε2 -phages were more virulent compared to their ancestors. Analysis of the genetic sequences of the ε2 -phages with the broadest host range reveals that they are mosaic intercrossings of 2–3 ancestor phages. The recombination sites are distributed over the whole length of the genome. All ε2 -phages are devoid of genes conferring lysogeny, antibiotic resistance, or virulence. Overall, this study shows that ε2 -phages are remarkably more suitable than the wild-type phages for phage therapy. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
7. ε 2 -Phages Are Naturally Bred and Have a Vastly Improved Host Range in Staphylococcus aureus over Wild Type Phages.
- Author
-
Sáez Moreno, David, Visram, Zehra, Mutti, Michele, Restrepo-Córdoba, Marcela, Hartmann, Susana, Kremers, Ana Isabel, Tišáková, Lenka, Schertler, Susanne, Wittmann, Johannes, Kalali, Benham, Monecke, Stefan, Ehricht, Ralf, Resch, Grégory, and Corsini, Lorenzo
- Subjects
- *
BACTERIOPHAGE typing , *DRUG resistance in bacteria , *METHICILLIN-resistant staphylococcus aureus , *STAPHYLOCOCCUS aureus , *BACTERIOPHAGES , *DETECTION limit - Abstract
Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for S. aureus infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 S. aureus strains (MRSA/MSSA) composed to reflect the prevalence of S. aureus clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%. We also measured what we called the kinetic host range (KHR), i.e., the percentage of strains for which growth in suspension was suppressed for 24 h. The KHR of the wild type phages ranged from 2% to 49%, substantially lower than the PHRs. To improve the KHR and other key pharmaceutical properties, we bred the phages by mixing and propagating cocktails on a subset of S. aureus strains. These bred phages, which we termed evolution-squared (ε2) phages, have broader KHRs up to 64% and increased virulence compared to the ancestors. The ε2-phages with the broadest KHR have genomes intercrossed from up to three different ancestors. We composed a cocktail of three ε2-phages with an overall KHR of 92% and PHR of 96% on 110 S. aureus strains and called it PM-399. PM-399 has a lower propensity to resistance formation than the standard of care antibiotics vancomycin, rifampicin, or their combination, and no resistance was observed in laboratory settings (detection limit: 1 cell in 1011). In summary, ε2-phages and, in particular PM-399, are promising candidates for an alternative treatment of S. aureus infections. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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