Barth Stefanie A, Peters Martin, Mormann Sascha, Möbius Petra, Calvelage Sten, Brangsch Hanka
Friedrich-Loeffler-Institut- Federal Research Institute for Animal Health (FLI), Institute of Molecular Pathogenesis (IMP), Jena, Germany.
National Reference Laboratory for Bovine Tuberculosis, Jena, Germany.
BMC Genomics. 2025 Aug 11;26(1):741. doi: 10.1186/s12864-025-11893-3.
Among the non-tuberculous mycobacteria, Mycobacterium (M.) avium are important pathogens for humans and/or animals. Currently, there are four M. avium subspecies: subsp. hominissuis (Mah), subsp. paratuberculosis (Map), subsp. avium (Maa), and subsp. silvaticum (Mas). While sufficient data is available for the first three mentioned, only few reports exist on the isolation, epidemiology and even less on the genetic equipment of Mas.
Here, Mas was isolated from an Egyptian goose that died of avian tuberculosis. Subspecies identification was based on the presence of IS901 and IS1245 as well as Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeat analysis demonstrating Mas specific profile INMV99 profile. During cultural isolation, Mas showed preference for media with mycobactin supplementation but was not limited to mycobactin-containing media. A closed genome sequence was assembled using short- and long-read sequencing technology. The genome sequence consisted of one circular chromosome of 4.84 Mb (GC content 69.3%) and no plasmid. It was highly similar to the only other available Mas sequence (ANI 99.98%, GGDC 99.7%) and eight Maa sequences (ANI ≥99.88%, GGDC ≥98.9%), although all Maa genomes were larger (approx. 5 Mb). In silico prediction of the metabolic pathways and gene content found that all Maa but no Mas should be able to synthetize ergothioneine and the carotenoid neurosporene. The analysis of the mycobactin cluster mbt-1 made it obvious that in Mas two of the eleven mbt genes (mbtB and mbtE) were probably dysfunctional due frameshift-based disruptions.
The first complete, high quality, closed genome sequence of a Mas isolate closes a knowledge gap. Even if the collection of further genome sequences is considered necessary, the now existing data set already enables a deeper analysis of M. avium. The found differences in the Mas gene content compared to the closest relative Maa seem to be stable and independent of spatial (France, UK, Germany) and temporal (>40 years) differences on their isolation. These data thus call into question the demand for merging the two subspecies Maa and Mas into one, but further genome sequences from other Mas strains are needed to answer this question conclusively.
在非结核分枝杆菌中，鸟分枝杆菌是人类和/或动物的重要病原体。目前，鸟分枝杆菌有四个亚种：人型亚种（Mah）、副结核亚种（Map）、鸟亚种（Maa）和森林亚种（Mas）。虽然关于前三个亚种有足够的数据，但关于Mas的分离、流行病学，甚至其基因组成的报道却很少。
在这里，Mas是从一只死于禽结核病的埃及鹅中分离出来的。亚种鉴定基于IS901和IS1245的存在以及分枝杆菌散布重复单位-可变数目串联重复分析，显示出Mas特异性的INMV99图谱。在培养分离过程中，Mas表现出对添加分枝杆菌生长素的培养基有偏好，但不限于含分枝杆菌生长素的培养基。使用短读长和长读长测序技术组装了一个封闭的基因组序列。基因组序列由一条4.84 Mb的环状染色体（GC含量69.3%）组成，没有质粒。它与唯一可用的另一个Mas序列高度相似（ANI 99.98%，GGDC 99.7%），与八个Maa序列也高度相似（ANI≥99.88%，GGDC≥98.9%），尽管所有Maa基因组都更大（约5 Mb）。对代谢途径和基因含量的电子预测发现，所有Maa菌株但没有Mas菌株应该能够合成麦角硫因和类胡萝卜素神经孢素。对分枝杆菌生长素簇mbt-1的分析表明，在Mas中，11个mbt基因中的两个（mbtB和mbtE）可能由于移码突变而功能失调。
Mas分离株的首个完整、高质量、封闭的基因组序列填补了知识空白。即使认为有必要收集更多的基因组序列，现有的数据集已经能够对鸟分枝杆菌进行更深入的分析。与最接近的亲缘种Maa相比，在Mas基因含量中发现的差异似乎是稳定的，且与它们分离时的空间（法国、英国、德国）和时间（>40年）差异无关。因此，这些数据对将Maa和Mas这两个亚种合并为一个亚种的需求提出了质疑，但需要来自其他Mas菌株的更多基因组序列才能最终回答这个问题。
