Genome-Wide Analysis of the Emerging Infection with <em>Mycobacterium avium</em> Subspecies <em>paratuberculosis</em> in the Arabian Camels (<em>Camelus dromedarius</em>)

Mycobacterium avium subspecies paratuberculosis (M. ap) is the causative agent of paratuberculosis or Johne's disease (JD) in herbivores with potential involvement in cases of Crohn's disease in humans. JD is spread worldwide and is economically important for both beef and dairy industries. Generally, pathogenic ovine strains (M. ap-S) are mainly found in sheep while bovine strains (M. ap-C) infect other ruminants (e.g. cattle, goat, deer), as well as sheep. In an effort to characterize this emerging infection in dromedary/Arabian camels, we successfully cultured M. ap from several samples collected from infected camels suffering from chronic, intermittent diarrhea suggestive of JD. Gene-based typing of isolates indicated that all isolates belong to sheep lineage of strains of M. ap (M. ap-S), suggesting a putative transmission from infected sheep herds. Screening sheep and goat herds associated with camels identified the circulation of this type in sheep but not goats. The current genome-wide analysis recognizes these camel isolates as a sub-lineage of the sheep strain with a significant number of single nucleotide polymorphisms (SNPs) between sheep and camel isolates (∼1000 SNPs). Such polymorphism could represent geographical differences among isolates or host adaptation of M. ap during camel infection. To our knowledge, this is the first attempt to examine the genomic basis of this emerging infection in camels with implications on the evolution of this important pathogen. The sequenced genomes of M. ap isolates from camels will further assist our efforts to understand JD pathogenesis and the dynamic of disease transmission across animal species.鸟分枝杆菌副结核亚种（Mycobacterium avium subsp. paratuberculosis，缩写M. ap）是草食动物副结核病（又称约翰氏病，JD）的致病菌，同时可能与人类克罗恩病的发病相关。JD在全球范围内广泛传播，对肉牛和乳品产业均具有重要的经济影响。通常而言，绵羊源致病性菌株（M. ap-S）主要分离自绵羊，而牛源菌株（M. ap-C）可感染其他反刍动物（如牛、山羊、鹿），亦可感染绵羊。为了表征单峰驼/阿拉伯骆驼中这一新兴感染性疾病，我们从多份来自患有表现为疑似约翰氏病的慢性间歇性腹泻的受感染骆驼的样本中成功分离培养出M. ap。对分离株进行基因分型的结果显示，所有分离株均属于M. ap绵羊谱系（M. ap-S），提示该病原菌可能由受感染的绵羊种群发生传播。对与骆驼同群的绵羊和山羊种群开展筛查后发现，该型菌株仅在绵羊中存在循环传播，未在山羊中检出。本次全基因组分析将这些骆驼分离株鉴定为绵羊菌株的一个亚谱系，且绵羊与骆驼分离株之间存在约1000个单核苷酸多态性（single nucleotide polymorphisms，缩写SNPs）。此类多态性可能反映了分离株间的地理差异，或是M. ap在骆驼宿主感染过程中发生的宿主适应性演化。据我们所知，本研究是首次针对骆驼中这一新兴感染性疾病的基因组基础展开的探索，其结果对阐释这一重要病原菌的演化具有重要参考价值。本次完成测序的骆驼源M. ap分离株基因组，将进一步助力我们解析JD的致病机制以及病原菌跨动物物种传播的动态过程。