Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection
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DOI:
10.1371/journal.pone.0029914
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发表时间:
2012-01-11
期刊:
影响因子:
3.7
通讯作者:
Philipp, Mario T.
Philipp, Mario T.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Embers, Monica E.;Barthold, Stephen W.;Philipp, Mario T.

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抗生素治疗后莱姆病患者症状的持续性及其原因仍然是一个激烈争议的问题。这里介绍的研究使用非人灵长类动物探索抗生素的功效。恒河猴感染B。Burgdorferi和一部分在4-6个月后接受积极的抗生素治疗。采用多种方法检测残留微生物,包括在猴子身上喂食实验室饲养的蜱(异种诊断)、培养、免疫荧光和PCR。对B的抗体反应。在所有治疗的动物中,纵向测量了伯氏特异性C6诊断肽,并下降。B。在处理动物的组织中检测到伯氏抗原、DNA和RNA。最后,通过异种诊断从治疗的猴子中回收了少量完整的螺旋体。这些结果表明,B.在灵长类宿主中,伯氏螺旋体可以耐受在传播后施用的抗生素治疗。虽然B。不知道伯氏菌具有抗性机制,并且在体外对标准抗生素(强力霉素、头孢曲松)敏感,但在灵长类宿主中传播后似乎变得耐受。这一发现提出了重要的问题,即耐药持续者的致病性,以及它们是否会导致治疗后的症状。
The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic efficacy using nonhuman primates. Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4-6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis), culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys. These results demonstrate that B. burgdorferi can withstand antibiotic treatment, administered post-dissemination, in a primate host. Though B. burgdorferi is not known to possess resistance mechanisms and is susceptible to the standard antibiotics (doxycycline, ceftriaxone) in vitro, it appears to become tolerant post-dissemination in the primate host. This finding raises important questions about the pathogenicity of antibiotic-tolerant persisters and whether or not they can contribute to symptoms post-treatment.