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Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms

High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particula...

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Autores principales: Sanchez, Belkys C., Heckmann, Emmaline R., Green, Sabrina I., Clark, Justin R., Kaplan, Heidi B., Ramig, Robert F., Muldrew, Kenneth L., Hines-Munson, Casey, Skelton, Felicia, Trautner, Barbara W., Maresso, Anthony W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127763/
https://www.ncbi.nlm.nih.gov/pubmed/35620093
http://dx.doi.org/10.3389/fmicb.2022.796132
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author Sanchez, Belkys C.
Heckmann, Emmaline R.
Green, Sabrina I.
Clark, Justin R.
Kaplan, Heidi B.
Ramig, Robert F.
Muldrew, Kenneth L.
Hines-Munson, Casey
Skelton, Felicia
Trautner, Barbara W.
Maresso, Anthony W.
author_facet Sanchez, Belkys C.
Heckmann, Emmaline R.
Green, Sabrina I.
Clark, Justin R.
Kaplan, Heidi B.
Ramig, Robert F.
Muldrew, Kenneth L.
Hines-Munson, Casey
Skelton, Felicia
Trautner, Barbara W.
Maresso, Anthony W.
author_sort Sanchez, Belkys C.
collection PubMed
description High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was measured by an MTT assay that determines cell metabolic activity and by quantification of colony forming units. Nine phage decreased cell viability by >80% when added individually to biofilms of two E. coli strains in human urine. A phage cocktail comprising six phage lyses 82% of the strains in our E. coli library and is highly effective against young and old biofilms and against biofilms on silicon catheter materials. Using antibiotics together with our phage cocktail prevented or decreased emergence of E. coli resistant to phage in human urine. We created an anti-biofilm phage cocktail with broad host range against E. coli strains isolated from urine. These phage cocktails may have therapeutic potential against CAUTI.
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spelling pubmed-91277632022-05-25 Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms Sanchez, Belkys C. Heckmann, Emmaline R. Green, Sabrina I. Clark, Justin R. Kaplan, Heidi B. Ramig, Robert F. Muldrew, Kenneth L. Hines-Munson, Casey Skelton, Felicia Trautner, Barbara W. Maresso, Anthony W. Front Microbiol Microbiology High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was measured by an MTT assay that determines cell metabolic activity and by quantification of colony forming units. Nine phage decreased cell viability by >80% when added individually to biofilms of two E. coli strains in human urine. A phage cocktail comprising six phage lyses 82% of the strains in our E. coli library and is highly effective against young and old biofilms and against biofilms on silicon catheter materials. Using antibiotics together with our phage cocktail prevented or decreased emergence of E. coli resistant to phage in human urine. We created an anti-biofilm phage cocktail with broad host range against E. coli strains isolated from urine. These phage cocktails may have therapeutic potential against CAUTI. Frontiers Media S.A. 2022-05-10 /pmc/articles/PMC9127763/ /pubmed/35620093 http://dx.doi.org/10.3389/fmicb.2022.796132 Text en Copyright © 2022 Sanchez, Heckmann, Green, Clark, Kaplan, Ramig, Muldrew, Hines-Munson, Skelton, Trautner and Maresso. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Sanchez, Belkys C.
Heckmann, Emmaline R.
Green, Sabrina I.
Clark, Justin R.
Kaplan, Heidi B.
Ramig, Robert F.
Muldrew, Kenneth L.
Hines-Munson, Casey
Skelton, Felicia
Trautner, Barbara W.
Maresso, Anthony W.
Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms
title Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms
title_full Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms
title_fullStr Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms
title_full_unstemmed Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms
title_short Development of Phage Cocktails to Treat E. coli Catheter-Associated Urinary Tract Infection and Associated Biofilms
title_sort development of phage cocktails to treat e. coli catheter-associated urinary tract infection and associated biofilms
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127763/
https://www.ncbi.nlm.nih.gov/pubmed/35620093
http://dx.doi.org/10.3389/fmicb.2022.796132
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