Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL <i>Escherichia coli</i>

<b>Background/Objectives:</b> Bacteriophage therapy represents a promising strategy to combat multidrug-resistant pathogens, such as <i>Escherichia coli</i>. In this study, we explored the effects of a bacteriophage infection on an Extended Spectrum Beta-Lactamase (ESBL) posi...

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Main Authors: Árpád Rózsa, László Orosz, Nikoletta Szemerédi, Gabriella Spengler, Gábor Kecskeméti, Otília Vágó, Károly Péter Sárvári, Diana Szabó, Zoltán Szabó, Katalin Burián, Dezső Péter Virok
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Language:English
Published: MDPI AG 2025-01-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/1/76
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author Árpád Rózsa
László Orosz
Nikoletta Szemerédi
Gabriella Spengler
Gábor Kecskeméti
Otília Vágó
Károly Péter Sárvári
Diana Szabó
Zoltán Szabó
Katalin Burián
Dezső Péter Virok
author_facet Árpád Rózsa
László Orosz
Nikoletta Szemerédi
Gabriella Spengler
Gábor Kecskeméti
Otília Vágó
Károly Péter Sárvári
Diana Szabó
Zoltán Szabó
Katalin Burián
Dezső Péter Virok
author_sort Árpád Rózsa
collection DOAJ
description <b>Background/Objectives:</b> Bacteriophage therapy represents a promising strategy to combat multidrug-resistant pathogens, such as <i>Escherichia coli</i>. In this study, we explored the effects of a bacteriophage infection on an Extended Spectrum Beta-Lactamase (ESBL) positive <i>E. coli</i> isolate. <b>Methods:</b> We used next generation sequencing, proteomics and phenotypic screens to investigate the effect of bacteriophage infections on <i>E. coli</i> metabolism and resistance phenotypes. <b>Results:</b> The bacteriophage infection led to notable alterations in colony morphology, indicating profound changes in bacterial metabolism. Proteomic analysis revealed significant shifts in protein expression, with 65 proteins upregulated and 246 downregulated post-infection. The downregulated proteins were involved in various metabolic pathways, including nucleic acid, protein and lipid metabolism, and iron acquisition. Bacteriophage treatment also led to increased bacterial membrane permeability. Altogether, these alterations in bacterial metabolism and membrane permeability may lead to a general reduction in antibiotic resistance. Indeed, the bacteriophage-infected <i>E. coli</i> exhibited increased sensitivity to various classes of antibiotics, including beta-lactams, fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides. <b>Conclusions:</b> Our findings highlight the potential of bacteriophage therapy as an adjunct to existing antibiotics, enhancing their efficacy against resistant strains.
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spelling doaj-art-267a03f2d96a438e896c39aa8d9cf8c42025-01-24T13:18:52ZengMDPI AGAntibiotics2079-63822025-01-011417610.3390/antibiotics14010076Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL <i>Escherichia coli</i>Árpád Rózsa0László Orosz1Nikoletta Szemerédi2Gabriella Spengler3Gábor Kecskeméti4Otília Vágó5Károly Péter Sárvári6Diana Szabó7Zoltán Szabó8Katalin Burián9Dezső Péter Virok10Pándy Kálmán County Hospital, Semmelweis Str. 1, H-5700 Gyula, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, HungaryDepartment of Medical Chemistry, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Dóm Sq. 8, H-6720 Szeged, HungaryPándy Kálmán County Hospital, Semmelweis Str. 1, H-5700 Gyula, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, HungaryDepartment of Oto-Rhino-Laryngology and Head & Neck Surgery, University of Szeged, Tisza Lajos Str. 111, H-6724 Szeged, HungaryDepartment of Medical Chemistry, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Dóm Sq. 8, H-6720 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, Hungary<b>Background/Objectives:</b> Bacteriophage therapy represents a promising strategy to combat multidrug-resistant pathogens, such as <i>Escherichia coli</i>. In this study, we explored the effects of a bacteriophage infection on an Extended Spectrum Beta-Lactamase (ESBL) positive <i>E. coli</i> isolate. <b>Methods:</b> We used next generation sequencing, proteomics and phenotypic screens to investigate the effect of bacteriophage infections on <i>E. coli</i> metabolism and resistance phenotypes. <b>Results:</b> The bacteriophage infection led to notable alterations in colony morphology, indicating profound changes in bacterial metabolism. Proteomic analysis revealed significant shifts in protein expression, with 65 proteins upregulated and 246 downregulated post-infection. The downregulated proteins were involved in various metabolic pathways, including nucleic acid, protein and lipid metabolism, and iron acquisition. Bacteriophage treatment also led to increased bacterial membrane permeability. Altogether, these alterations in bacterial metabolism and membrane permeability may lead to a general reduction in antibiotic resistance. Indeed, the bacteriophage-infected <i>E. coli</i> exhibited increased sensitivity to various classes of antibiotics, including beta-lactams, fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides. <b>Conclusions:</b> Our findings highlight the potential of bacteriophage therapy as an adjunct to existing antibiotics, enhancing their efficacy against resistant strains.https://www.mdpi.com/2079-6382/14/1/76bacteriophagecocktailantibioticresistance<i>Escherichia</i>siderophore
spellingShingle Árpád Rózsa
László Orosz
Nikoletta Szemerédi
Gabriella Spengler
Gábor Kecskeméti
Otília Vágó
Károly Péter Sárvári
Diana Szabó
Zoltán Szabó
Katalin Burián
Dezső Péter Virok
Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL <i>Escherichia coli</i>
Antibiotics
bacteriophage
cocktail
antibiotic
resistance
<i>Escherichia</i>
siderophore
title Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL <i>Escherichia coli</i>
title_full Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL <i>Escherichia coli</i>
title_fullStr Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL <i>Escherichia coli</i>
title_full_unstemmed Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL <i>Escherichia coli</i>
title_short Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL <i>Escherichia coli</i>
title_sort bacteriophage treatment induces phenotype switching and alters antibiotic resistance of esbl i escherichia coli i
topic bacteriophage
cocktail
antibiotic
resistance
<i>Escherichia</i>
siderophore
url https://www.mdpi.com/2079-6382/14/1/76
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