Identification of Mycobacterium avium pathogenicity island important for macrophage and amoeba infection
Identification of Mycobacterium avium pathogenicity island important for macrophage and amoeba infection
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DOI：
10.1073/pnas.0610746104
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发表时间：
2007-06-26
影响因子：
11.1
通讯作者：
Bermudez, Luiz E.
中科院分区：
文献类型：
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作者：
Danelishvili, Lia;Wu, Martin;Bermudez, Luiz E.
感染巨噬细胞的能力是许多分枝杆菌物种的共同特征。鸟分枝杆菌、结核分枝杆菌和堪萨斯分枝杆菌通过补体受体CR1、CR3、CR4和甘露糖受体进入巨噬细胞。为了确定与巨噬细胞摄取细菌有关的禽类支原体基因和宿主细胞途径，我们筛选了一个不能进入巨噬细胞的禽类支原体转座子突变文库。选择了摄取受损的克隆。对6个绵羊乳杆菌克隆的序列分析表明，1个基因参与糖肽脂生物合成，1个基因编码与绵羊乳杆菌亚种同源的保守的膜蛋白。副结核MAP2446c基因和其他四个属于同一染色体区域的基因。对染色体区域的分析显示，在两个tRNA序列之间插入了一个致病岛，G+C含量为58%，而禽类支原体基因组中G+C含量为69%。该区域是禽分枝杆菌所特有的，在结核分枝杆菌或副结核分枝杆菌中不存在。虽然突变体在与巨噬细胞膜的结合方面与WT细菌没有不同，但感染1h后对巨噬细胞蛋白质的分析显示，突变体缺乏摄取某些蛋白质的磷酸化能力。为了了解鸟分枝杆菌与两个进化上不同的宿主的相互作用，对突变体入侵卡氏棘阿米巴进行了评估。突变体入侵这两个细胞的能力缺陷非常相似，这表明禽类分枝杆菌可能进化出了进入阿米巴和人类巨噬细胞的机制。
The ability to infect macrophages is a common characteristic shared among many mycobacterial species. Mycobacterium avium, Mycobacterium tuberculosis, and Mycobacterium kansasii enter macrophages, using the complement receptors CR1, CR3, CR4, and the mannose receptor. To identify M. avium genes and host cell pathways involved in the bacterial uptake by macrophages, we screened a M. avium transposon mutant library for the inability to enter macrophages. Uptake-impaired clones were selected. Sequence of six M. avium clones identified one gene involved in glycopeptidolipid biosynthesis, one gene encoding the conserved membrane protein homologue to the M. avium subsp. paratuberculosis MAP2446c gene and four others belonging to the same region of the chromosome. Analysis of the chromosome region revealed a pathogenicity island inserted between two tRNA sequences with 58% of G+C content versus 69% in the M. avium genome. The region is unique for M. avium and is not present in M. tuberculosis or M. paratuberculosis. Although the mutants did not differ from the WT bacterium regarding the binding to macrophage cell membrane, analysis of macrophage proteins after 1 h infection revealed a deficiency in the mutant to phosphorylate certain proteins on uptake. To understand M. avium interaction with two evolutionarily distinct hosts, the mutants were evaluated for Acanthamoeba castellanii invasion. The defect in the ability of the mutants to invade both cells was highly similar, suggesting that M. avium might have evolved mechanisms that are used to enter amoebas and human macrophages.