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饮食诱导的肥胖不改变替加环素对小鼠莱姆病的治疗效果。

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

作者信息

Pětrošová Helena, Eshghi Azad, Anjum Zoha, Zlotnikov Nataliya, Cameron Caroline E, Moriarty Tara J

机构信息

Matrix Dynamics Group, Faculty of Dentistry, University of Toronto Toronto, ON, Canada.

Department of Biochemistry and Microbiology, University of Victoria Victoria, BC, Canada.

出版信息

Front Microbiol. 2017 Feb 24;8:292. doi: 10.3389/fmicb.2017.00292. eCollection 2017.

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, . Diet-induced obese C3H/HeN mice and normal-weight controls were infected with , 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, -specific IgG production was monitored throughout the experiment. Tigecycline treatment was ineffective in reducing 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 -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 were detected in any antibiotic-treated group. In conclusion, obesity was associated with attenuated and delayed humoral immune responses to , but did not affect efficacy of antibiotic treatment.

摘要

肥胖个体更容易受到感染,这是由于对多种细菌病原体的易感性增加。此外,肥胖会因药物药代动力学的变化而改变抗生素治疗效果,这可能导致剂量不足。然而,关于肥胖背景下细菌感染治疗的研究很少。为了填补这一研究空白,我们评估了抗生素治疗对感染莱姆病病原体的饮食诱导肥胖小鼠的疗效。饮食诱导肥胖的C3H/HeN小鼠和正常体重对照感染后,在感染急性期用两剂替加环素进行治疗,剂量根据饮食诱导肥胖小鼠和正常体重小鼠的体重进行调整。治疗1个月后,通过从组织中培养细菌、测量莱姆心肌炎的严重程度以及量化十个组织中的细菌DNA清除率来评估抗生素治疗效果。此外,在整个实验过程中监测特异性IgG的产生。替加环素治疗在减少大脑中的DNA拷贝数方面无效。然而,无论用于治疗的替加环素剂量如何,饮食诱导肥胖均未影响任何组织中依赖抗生素的细菌DNA清除。与模拟治疗的正常体重动物相比,模拟治疗的饮食诱导肥胖小鼠中特异性IgG的产生延迟且减弱,但抗生素治疗后各实验组之间无差异。在任何抗生素治疗组中均未检测到心肌炎或可培养的细菌。总之,肥胖与对的体液免疫反应减弱和延迟有关,但不影响抗生素治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd09/5323460/7f964a4beb26/fmicb-08-00292-g001.jpg

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