Real-Time PCR Research and Diagnostic Core Facility, School of Veterinary Medicine, University of California at Davis, Davis, California, USA
Comparative Pathology Laboratory, School of Veterinary Medicine, University of California at Davis, Davis, California, USA.
Infect Immun. 2019 Sep 19;87(10). doi: 10.1128/IAI.00442-19. Print 2019 Oct.
A basic feature of infection caused by , the etiological agent of Lyme borreliosis, is that persistent infection is the rule in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge. There is growing experimental evidence that viable but noncultivable spirochetes persist following treatment with several different antimicrobial agents. The current study utilized the mouse model to evaluate if persistence occurs following antimicrobial treatment in disease-susceptible (C3H/HeJ [C3H]) and disease-resistant (C57BL/6 [B6]) mouse strains infected with strains N40 and B31 and to confirm the generality of this phenomenon, as well as to assess the persisters' clinical relevance. The status of infection was evaluated at 12 and 18 months after treatment. The results demonstrated that persistent spirochetes remain viable for up to 18 months following treatment, as well as being noncultivable. The phenomenon of persistence in disease-susceptible C3H mice is equally evident in disease-resistant B6 mice and not unique to any particular strain. The results also demonstrate that, following antimicrobial treatment, both strains of , N40 and B31, lose one or more plasmids. The study demonstrated that noncultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection. The clinical relevance of persistent spirochetes beyond 18 months following antimicrobial treatment requires further studies in other animal models.
伯氏疏螺旋体感染的一个基本特征是,其许多宿主中持续性感染是普遍现象。能够持续存在并逃避宿主免疫清除是有效抗菌治疗的挑战。治疗失败与持续存在细胞之间的联系已开始显现。越来越多的实验证据表明,在使用几种不同的抗菌药物治疗后,活但不可培养的螺旋体仍然存在。本研究利用小鼠模型评估了在易感染(C3H/HeJ [C3H])和抗感染(C57BL/6 [B6])的感染株 N40 和 B31 感染的小鼠中,在抗菌治疗后是否会发生持续性感染,并确认这种现象的普遍性,以及评估持续性细胞的临床相关性。在治疗后 12 个月和 18 个月评估感染状态。结果表明,在治疗后长达 18 个月,持续存在的螺旋体仍然存活且无法培养。在易感 C3H 小鼠中持续性感染的现象在抗感染 B6 小鼠中同样明显,且并非任何特定的 菌株所特有。结果还表明,在抗菌治疗后,N40 和 B31 两种 菌株均失去一个或多个质粒。该研究表明,在抗菌治疗后,非可培养的螺旋体可以在宿主中持续存在很长时间,但在慢性感染的小鼠模型中并未证明其临床相关性。在抗菌治疗后 18 个月后,持续存在的螺旋体的临床相关性需要在其他动物模型中进一步研究。