Comparative Genomics of Mycoplasma bovis Strains Reveals That Decreased Virulence with Increasing Passages Might Correlate with Potential Virulence-Related Factors.
Comparative Genomics of Mycoplasma bovis Strains Reveals That Decreased Virulence with Increasing Passages Might Correlate with Potential Virulence-Related Factors.
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DOI：
10.3389/fcimb.2017.00177
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发表时间：
2017
影响因子：
5.7
通讯作者：
Guo A
中科院分区：
文献类型：
--
作者：
Rasheed MA;Qi J;Zhu X;Chenfei H;Menghwar H;Khan FA;Zhao G;Zubair M;Hu C;Chen Y;Chen H;Guo A
牛支原体是全世界牛呼吸道疾病的重要原因。为了了解其毒力机制，我们对三种减毒牛分枝杆菌菌株 P115、P150 和 P180 进行了测序，这些菌株分别在体外传代 115、150 和 180 次，并表现出逐渐降低的毒力。对野生型牛支原体HB0801(P1)菌株和P115、P150和P180菌株进行比较基因组学分析，在传代菌株中检测到1个14.2 kb的缺失区域，涵盖14个基因。此外，还检测到 46 个无义单核苷酸多态性和插入缺失，证实更多的传代会导致更多的突变。随后对旁系同源物、代谢途径、蛋白质-蛋白质相互作用、分泌蛋白、功能保守结构域和毒力相关因素进行的集体生物信息学分析确定了 11 个可能导致传代菌株减毒增加的基因。这些基因编码抗坏血酸特异性磷酸转移酶系统酶 IIB 和 IIA 成分、烯醇酶、L-乳酸脱氢酶、丙酮酸激酶、甘油和多糖 ATP 结合盒转运蛋白、ATP 结合蛋白、NADH 脱氢酶、磷酸乙酰转移酶、转酮醇酶和可变表面蛋白。结果显示，15 个基因在 15 条代谢途径中富集，其中包括上述编码丙酮酸激酶、转酮醇酶、烯醇化酶和 L-乳酸脱氢酶的基因。代表从 P1 到 P180 的七次传代的牛分枝杆菌菌株中的过氧化氢 (H2O2) 产量随着传代次数的增加和衰减的增加而逐渐减少。然而，14.2-kb 删除区域内 8 个单独基因特异的 8 个突变体并未表现出 H2O2 产生的改变。这些结果丰富了牛分枝杆菌基因组数据库，并增加了我们对牛分枝杆菌毒力机制的理解。
Mycoplasma bovis is an important cause of bovine respiratory disease worldwide. To understand its virulence mechanisms, we sequenced three attenuated M. bovis strains, P115, P150, and P180, which were passaged in vitro 115, 150, and 180 times, respectively, and exhibited progressively decreasing virulence. Comparative genomics was performed among the wild-type M. bovis HB0801 (P1) strain and the P115, P150, and P180 strains, and one 14.2-kb deleted region covering 14 genes was detected in the passaged strains. Additionally, 46 non-sense single-nucleotide polymorphisms and indels were detected, which confirmed that more passages result in more mutations. A subsequent collective bioinformatics analysis of paralogs, metabolic pathways, protein-protein interactions, secretory proteins, functionally conserved domains, and virulence-related factors identified 11 genes that likely contributed to the increased attenuation in the passaged strains. These genes encode ascorbate-specific phosphotransferase system enzyme IIB and IIA components, enolase, L-lactate dehydrogenase, pyruvate kinase, glycerol, and multiple sugar ATP-binding cassette transporters, ATP binding proteins, NADH dehydrogenase, phosphate acetyltransferase, transketolase, and a variable surface protein. Fifteen genes were shown to be enriched in 15 metabolic pathways, and they included the aforementioned genes encoding pyruvate kinase, transketolase, enolase, and L-lactate dehydrogenase. Hydrogen peroxide (H2O2) production in M. bovis strains representing seven passages from P1 to P180 decreased progressively with increasing numbers of passages and increased attenuation. However, eight mutants specific to eight individual genes within the 14.2-kb deleted region did not exhibit altered H2O2 production. These results enrich the M. bovis genomics database, and they increase our understanding of the mechanisms underlying M. bovis virulence.