Data_Sheet_3_Genomic analysis of Mycobacterium brumae sustains its nonpathogenic and immunogenic phenotype.XLSX

Mycobacterium brumae is a rapid-growing, non-pathogenic Mycobacterium species, originally isolated from environmental and human samples in Barcelona, Spain. Mycobacterium brumae is not pathogenic and it’s in vitro phenotype and immunogenic properties have been well characterized. However, the knowledge of its underlying genetic composition is still incomplete. In this study, we first describe the 4 Mb genome of the M. brumae type strain ATCC 51384T assembling PacBio reads, and second, we assess the low intraspecies variability by comparing the type strain with Illumina reads from three additional strains. Mycobacterium brumae genome is composed of a circular chromosome with a high GC content of 69.2% and containing 3,791 CDSs, 97 pseudogenes, one prophage and no CRISPR loci. Mycobacterium brumae has shown no pathogenic potential in in vivo experiments, and our genomic analysis confirms its phylogenetic position with other non-pathogenic and rapid growing mycobacteria. Accordingly, we determined the absence of virulence-related genes, such as ESX-1 locus and most PE/PPE genes, among others. Although the immunogenic potential of M. brumae was proved to be as high as Mycobacterium bovis BCG, the only mycobacteria licensed to treat cancer, the genomic content of M. tuberculosis T cell and B cell antigens in M. brumae genome is considerably lower than those antigens present in M. bovis BCG genome. Overall, this work provides relevant genomic data on one of the species of the mycobacterial genus with high therapeutic potential.

布鲁玛分枝杆菌（Mycobacterium brumae）是一类快速生长、无致病性的分枝杆菌菌种，最初分离自西班牙巴塞罗那的环境样本与人类样本。该菌种不具有致病性，其体外表型与免疫原性特征已得到充分表征，但目前对其潜在遗传组成的认知仍不完善。本研究首先通过组装PacBio测序读段，解析了布鲁玛分枝杆菌模式菌株ATCC 51384^T的4 Mb基因组；其次，通过将该模式菌株与另外3株菌株的Illumina测序读段进行比对，评估了其较低的种内变异程度。布鲁玛分枝杆菌基因组由一条环状染色体构成，GC含量达69.2%，共包含3791个编码序列（Coding Sequence, CDS）、97个假基因（pseudogene）、1个前噬菌体（prophage），且无CRISPR位点（CRISPR）。布鲁玛分枝杆菌在体内实验中未表现出致病潜力，本研究的基因组分析结果证实，其系统发育地位与其他无致病性的快速生长分枝杆菌相符；据此我们确认，其基因组中不存在ESX-1位点以及绝大多数PE/PPE基因等毒力相关基因。尽管已有研究证实，布鲁玛分枝杆菌的免疫原潜力可与目前唯一获批用于癌症治疗的分枝杆菌——牛分枝杆菌卡介苗（Mycobacterium bovis BCG）相媲美，但其基因组中结核分枝杆菌（Mycobacterium tuberculosis）T细胞与B细胞抗原的编码基因数量，远低于牛分枝杆菌卡介苗基因组中的同类抗原基因。综上，本研究为分枝杆菌属中一类具有高治疗潜力的菌种提供了重要的基因组数据支撑。