Sassi Mohamed, Drancourt Michel
Aix Marseille Université, URMITE, UMR63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France.
BMC Genomics. 2014 May 12;15(1):359. doi: 10.1186/1471-2164-15-359.
Mycobacterium abscessus complex, the third most frequent mycobacterial complex responsible for community- and health care-associated infections in developed countries, comprises of M. abscessus subsp. abscessus and M. abscessus subsp. bolletii reviously referred as Mycobacterium bolletii and Mycobacterium massiliense. The diversity of this group of opportunistic pathogens is poorly described.
In-depth analysis of 14 published M. abscessus complex genomes found a pan-genome of 6,153 proteins and core-genome of 3,947 (64.1%) proteins, indicating a non-conservative genome. Analysing the average percentage of amino-acid sequence identity (from 94.19% to 98.58%) discriminates three main clusters C1, C2 and C3: C1 comprises strains belonging to M. abscessus, C2 comprises strains belonging to M. massiliense and C3 comprises strains belonging to M. bolletii; and two sub-clusters in clusters C2 and C3. The phylogenomic network confirms these three clusters. The genome length (from 4.8 to 5.51-Mb) varies from 5.07-Mb in C1, 4.89-Mb in C2A, 5.01-Mb in C2B and 5.28-Mb in C3. The mean number of prophage regions (from 0 to 7) is 2 in C1; 1.33 in C2A; 3.5 in C2B and five in C3. A total of 36 genes are uniquely present in C1, 15 in C2 and 15 in C3. These genes could be used for the detection and identification of organisms in each cluster. Further, the mean number of host-interaction factors (including PE, PPE, LpqH, MCE, Yrbe and type VII secretion system ESX3 and ESX4) varies from 70 in cluster C1, 80 in cluster C2A, 74 in cluster C2B and 93 in clusters C3A and C3B. No significant differences in antibiotic resistance genes were observed between clusters, in contrast to previously reported in-vitro patterns of drug resistance. They encode both penicillin-binding proteins targeted by β-lactam antibiotics and an Ambler class A β-lactamase for which inhibitors exist.
Our comparative analysis indicates that M. abscessus complex comprises three genomospecies, corresponding to M. abscessus, M. bolletii, and M. massiliense. The genomics data here reported indicate differences in virulence of medical interest; and suggest targets for the refined detection and identification of M. abscessus.
脓肿分枝杆菌复合群是发达国家社区和医疗保健相关感染的第三大常见分枝杆菌复合群,由脓肿分枝杆菌亚种脓肿分枝杆菌和脓肿分枝杆菌亚种博列蒂分枝杆菌组成,后者以前被称为博列蒂分枝杆菌和马西利亚分枝杆菌。对这组机会性病原体的多样性描述甚少。
对14个已发表的脓肿分枝杆菌复合群基因组进行深入分析,发现泛基因组有6153个蛋白质,核心基因组有3947个(64.1%)蛋白质,表明其基因组不保守。分析氨基酸序列同一性的平均百分比(从94.19%到98.58%)可区分三个主要簇C1、C2和C3:C1包含脓肿分枝杆菌的菌株,C2包含马西利亚分枝杆菌的菌株,C3包含博列蒂分枝杆菌的菌株;以及C2和C3簇中的两个亚簇。系统发育网络证实了这三个簇。基因组长度(从4.8到5.51兆碱基)在C1中为5.07兆碱基,在C2A中为4.89兆碱基,在C2B中为5.01兆碱基,在C3中为5.28兆碱基。前噬菌体区域的平均数量(从0到7)在C1中为2个;在C2A中为1.33个;在C2B中为3.5个,在C3中为5个。共有36个基因仅存在于C1中,15个在C2中,15个在C3中。这些基因可用于检测和鉴定每个簇中的生物体。此外,宿主相互作用因子(包括PE、PPE、LpqH、MCE、Yrbe以及VII型分泌系统ESX3和ESX4)的平均数量在C1簇中为70个,在C2A簇中为80个,在C2B簇中为74个,在C3A和C3B簇中为93个。与先前报道的体外耐药模式相反,各簇之间未观察到抗生素耐药基因的显著差异。它们编码β-内酰胺抗生素靶向的青霉素结合蛋白以及存在抑制剂的A类安布勒β-内酰胺酶。
我们的比较分析表明,脓肿分枝杆菌复合群包括三个基因种,分别对应脓肿分枝杆菌、博列蒂分枝杆菌和马西利亚分枝杆菌。此处报告的基因组数据表明了具有医学意义的毒力差异;并为脓肿分枝杆菌的精确检测和鉴定提供了靶点。