Parrish Nicole, Vadlamudi Aravinda, Goldberg Neil
The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Meyer B1-193, Baltimore, Maryland USA.
Saint Joseph Medical Center, University of Maryland, Towson, Maryland USA.
Gut Pathog. 2017 Jun 10;9:34. doi: 10.1186/s13099-017-0183-z. eCollection 2017.
subspecies (MAP) is the causative agent of Johne's disease in ruminants and is associated with Crohn's disease (CD) in humans, although the latter remains controversial. In this study, we investigated the ability of MAP to adapt to anaerobic growth using the "Wayne" model of non-replicating persistence (NRP) developed for .
All strains adapted to anaerobiosis over time in a manner similar to that seen with MTB. Susceptibility to 12 antibiotics varied widely between strains under aerobic conditions. Under anaerobic conditions, no drugs caused significant growth inhibition (>0.5 log) except metronidazole, resulting in an average decrease of ~2 logs.
These results demonstrate that MAP is capable of adaptation to NRP similar to that observed for MTB with differential susceptibility to antibiotics under aerobic versus anaerobic conditions. Such findings have significant implications for our understanding of the pathogenesis of MAP in vivo and the treatment of CD should this organism be established as the causative agent.
副结核分枝杆菌(MAP)是反刍动物中约翰氏病的病原体,并且与人类的克罗恩病(CD)有关,尽管后者仍存在争议。在本研究中,我们使用为结核分枝杆菌(MTB)开发的非复制性持续存在(NRP)的“韦恩”模型,研究了MAP适应厌氧生长的能力。
所有菌株随着时间的推移以类似于MTB的方式适应了厌氧环境。在需氧条件下,各菌株对12种抗生素的敏感性差异很大。在厌氧条件下,除甲硝唑外,没有药物引起显著的生长抑制(>0.5个对数),导致平均下降约2个对数。
这些结果表明,MAP能够像MTB一样适应NRP,在需氧和厌氧条件下对抗生素的敏感性不同。这些发现对于我们理解MAP在体内的发病机制以及如果该生物体被确定为病原体时对CD的治疗具有重要意义。