title: Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease.
abstract: 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 withB. 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 reducingB. burgdorferiDNA 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 ofB. 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 cultivatableB. burgdorferiwere detected in any antibiotic-treated group. In conclusion, obesity was associated with attenuated and delayed humoral immune responses toB. burgdorferi, but did not affect efficacy of antibiotic treatment.
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto Toronto, ON, Canada.
authors.forename: Helena
authors.initials: H
authors.lastname: Pětrošová
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto Toronto, ON, Canada.
authors.forename: Azad
authors.initials: A
authors.lastname: Eshghi
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto Toronto, ON, Canada.
authors.forename: Zoha
authors.initials: Z
authors.lastname: Anjum
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto Toronto, ON, Canada.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Zlotnikov
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria Victoria, BC, Canada.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Cameron
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of TorontoToronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of TorontoToronto, ON, Canada.
authors.forename: Tara J
authors.initials: TJ
authors.lastname: Moriarty
keywords: Borrelia burgdorferi; Lyme disease; antibiotics; bacterial infection; diet-induced obesity; humoral response; obesity; tigecycline