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Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease

Obese individuals more frequently suffer from infections, as a result of increased susceptibility to a number of bacterial pathogens. Furthermore, obesity can alter antibiotic treatment efficacy due to changes in drug pharmacokinetics which can result in under-dosing. However, studies on the treatme...

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Autores principales: Pětrošová, Helena, Eshghi, Azad, Anjum, Zoha, Zlotnikov, Nataliya, Cameron, Caroline E., Moriarty, Tara J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323460/
https://www.ncbi.nlm.nih.gov/pubmed/28286500
http://dx.doi.org/10.3389/fmicb.2017.00292
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author Pětrošová, Helena
Eshghi, Azad
Anjum, Zoha
Zlotnikov, Nataliya
Cameron, Caroline E.
Moriarty, Tara J.
author_facet Pětrošová, Helena
Eshghi, Azad
Anjum, Zoha
Zlotnikov, Nataliya
Cameron, Caroline E.
Moriarty, Tara J.
author_sort Pětrošová, Helena
collection PubMed
description Obese individuals more frequently suffer from infections, as a result of increased susceptibility to a number of bacterial pathogens. Furthermore, obesity can alter antibiotic treatment efficacy due to changes in drug pharmacokinetics which can result in under-dosing. However, studies on the treatment of bacterial infections in the context of obesity are scarce. To address this research gap, we assessed efficacy of antibiotic treatment in diet-induced obese mice infected with the Lyme disease pathogen, Borrelia burgdorferi. Diet-induced obese C3H/HeN mice and normal-weight controls were infected with B. burgdorferi, and treated during the acute phase of infection with two doses of tigecycline, adjusted to the weights of diet-induced obese and normal-weight mice. Antibiotic treatment efficacy was assessed 1 month after the treatment by cultivating bacteria from tissues, measuring severity of Lyme carditis, and quantifying bacterial DNA clearance in ten tissues. In addition, B. burgdorferi-specific IgG production was monitored throughout the experiment. Tigecycline treatment was ineffective in reducing B. burgdorferi DNA copies in brain. However, diet-induced obesity did not affect antibiotic-dependent bacterial DNA clearance in any tissues, regardless of the tigecycline dose used for treatment. Production of B. burgdorferi-specific IgGs was delayed and attenuated in mock-treated diet-induced obese mice compared to mock-treated normal-weight animals, but did not differ among experimental groups following antibiotic treatment. No carditis or cultivatable B. burgdorferi were detected in any antibiotic-treated group. In conclusion, obesity was associated with attenuated and delayed humoral immune responses to B. burgdorferi, but did not affect efficacy of antibiotic treatment.
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spelling pubmed-53234602017-03-10 Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease Pětrošová, Helena Eshghi, Azad Anjum, Zoha Zlotnikov, Nataliya Cameron, Caroline E. Moriarty, Tara J. Front Microbiol Microbiology Obese individuals more frequently suffer from infections, as a result of increased susceptibility to a number of bacterial pathogens. Furthermore, obesity can alter antibiotic treatment efficacy due to changes in drug pharmacokinetics which can result in under-dosing. However, studies on the treatment of bacterial infections in the context of obesity are scarce. To address this research gap, we assessed efficacy of antibiotic treatment in diet-induced obese mice infected with the Lyme disease pathogen, Borrelia burgdorferi. Diet-induced obese C3H/HeN mice and normal-weight controls were infected with B. burgdorferi, and treated during the acute phase of infection with two doses of tigecycline, adjusted to the weights of diet-induced obese and normal-weight mice. Antibiotic treatment efficacy was assessed 1 month after the treatment by cultivating bacteria from tissues, measuring severity of Lyme carditis, and quantifying bacterial DNA clearance in ten tissues. In addition, B. burgdorferi-specific IgG production was monitored throughout the experiment. Tigecycline treatment was ineffective in reducing B. burgdorferi DNA copies in brain. However, diet-induced obesity did not affect antibiotic-dependent bacterial DNA clearance in any tissues, regardless of the tigecycline dose used for treatment. Production of B. burgdorferi-specific IgGs was delayed and attenuated in mock-treated diet-induced obese mice compared to mock-treated normal-weight animals, but did not differ among experimental groups following antibiotic treatment. No carditis or cultivatable B. burgdorferi were detected in any antibiotic-treated group. In conclusion, obesity was associated with attenuated and delayed humoral immune responses to B. burgdorferi, but did not affect efficacy of antibiotic treatment. Frontiers Media S.A. 2017-02-24 /pmc/articles/PMC5323460/ /pubmed/28286500 http://dx.doi.org/10.3389/fmicb.2017.00292 Text en Copyright © 2017 Pětrošová, Eshghi, Anjum, Zlotnikov, Cameron and Moriarty. http://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) or licensor 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
Pětrošová, Helena
Eshghi, Azad
Anjum, Zoha
Zlotnikov, Nataliya
Cameron, Caroline E.
Moriarty, Tara J.
Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease
title Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease
title_full Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease
title_fullStr Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease
title_full_unstemmed Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease
title_short Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease
title_sort diet-induced obesity does not alter tigecycline treatment efficacy in murine lyme disease
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323460/
https://www.ncbi.nlm.nih.gov/pubmed/28286500
http://dx.doi.org/10.3389/fmicb.2017.00292
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