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Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity

The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms...

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Autores principales: Goneau, Lee W., Hannan, Thomas J., MacPhee, Roderick A., Schwartz, Drew J., Macklaim, Jean M., Gloor, Gregory B., Razvi, Hassan, Reid, Gregor, Hultgren, Scott J., Burton, Jeremy P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453531/
https://www.ncbi.nlm.nih.gov/pubmed/25827417
http://dx.doi.org/10.1128/mBio.00356-15
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author Goneau, Lee W.
Hannan, Thomas J.
MacPhee, Roderick A.
Schwartz, Drew J.
Macklaim, Jean M.
Gloor, Gregory B.
Razvi, Hassan
Reid, Gregor
Hultgren, Scott J.
Burton, Jeremy P.
author_facet Goneau, Lee W.
Hannan, Thomas J.
MacPhee, Roderick A.
Schwartz, Drew J.
Macklaim, Jean M.
Gloor, Gregory B.
Razvi, Hassan
Reid, Gregor
Hultgren, Scott J.
Burton, Jeremy P.
author_sort Goneau, Lee W.
collection PubMed
description The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogens Staphylococcus saprophyticus and Escherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections.
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spelling pubmed-44535312015-06-03 Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity Goneau, Lee W. Hannan, Thomas J. MacPhee, Roderick A. Schwartz, Drew J. Macklaim, Jean M. Gloor, Gregory B. Razvi, Hassan Reid, Gregor Hultgren, Scott J. Burton, Jeremy P. mBio Research Article The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogens Staphylococcus saprophyticus and Escherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections. American Society of Microbiology 2015-03-31 /pmc/articles/PMC4453531/ /pubmed/25827417 http://dx.doi.org/10.1128/mBio.00356-15 Text en Copyright © 2015 Goneau et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Goneau, Lee W.
Hannan, Thomas J.
MacPhee, Roderick A.
Schwartz, Drew J.
Macklaim, Jean M.
Gloor, Gregory B.
Razvi, Hassan
Reid, Gregor
Hultgren, Scott J.
Burton, Jeremy P.
Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity
title Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity
title_full Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity
title_fullStr Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity
title_full_unstemmed Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity
title_short Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity
title_sort subinhibitory antibiotic therapy alters recurrent urinary tract infection pathogenesis through modulation of bacterial virulence and host immunity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453531/
https://www.ncbi.nlm.nih.gov/pubmed/25827417
http://dx.doi.org/10.1128/mBio.00356-15
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