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

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dc.contributor.authorPětrošová, Helena
dc.contributor.authorEshghi, Azad
dc.contributor.authorAnjum, Zoha
dc.contributor.authorZlotnikov, Nataliya
dc.contributor.authorCameron, Caroline E.
dc.contributor.authorMoriarty, Tara J.
dc.date.accessioned2018-08-02T17:51:09Z
dc.date.available2018-08-02T17:51:09Z
dc.date.copyright2017en_US
dc.date.issued2017-02
dc.description.abstractObese 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.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis study was funded by Premier Lyme and Tick-Borne Research Grants, Canadian Institutes of Health Research (CIHR) (MOP-11959), CIHR Bhagirath Singh Award (ICS-12398), Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN 401), Banting Research Foundation, Faculty of Dentistry Enrichment and Bertha Rosenstadt Endowment Funds and Canada Foundation for Innovation/Ontario Research Fund (CFI/ORF) (award 27881) to TM; NSERC Discovery grant (327186) and National Institutes of Health (NIH) Public Health Service grant (AI-051334) to CC. CC gratefully acknowledges the Canada Research Chair program for salary support. Postdoctoral fellowships: Heart and Stroke/Richard Lewar Centre of Excellence (HP), Ted Rogers Center for Heart Research Education Fund Fellowship (AE); Undergraduate fellowships: CIHR Mobility, musculoskeletal health and arthritis (ZA). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.en_US
dc.identifier.citationPětrošová, H.; Eshghi, A.; Anjum, Z.; Zlotnikov, N.; Cameron, C.E.; & Moriarty T.J. (2017). Diet-induced obesity does not alter tigecycline treatment efficacy murine lyme disease. Frontiers in Microbiology, 8, article 292. https://doi.org/10.3389/fmicb.2017.00292en_US
dc.identifier.urihttps://doi.org/10.3389/fmicb.2017.00292
dc.identifier.urihttp://hdl.handle.net/1828/9819
dc.language.isoenen_US
dc.publisherFrontiers in Microbiologyen_US
dc.subjectBorrelia burgdorferi
dc.subjectLyme disease
dc.subjectbacterial infection
dc.subjectantibiotics
dc.subjecttigecycline
dc.subjectobesity
dc.subjectdiet-induced obesity
dc.subjecthumoral response
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleDiet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Diseaseen_US
dc.typeArticleen_US

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