Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding
Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding
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DOI：
10.1073/pnas.0404817101
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发表时间：
2004-11-30
影响因子：
11.1
通讯作者：
Arnqvist, A
中科院分区：
文献类型：
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作者：
Bäckström, A;Lundberg, C;Arnqvist, A
幽门螺杆菌菌株在胃上皮粘附中的异质性被认为有助于生理多样性人群中的病原体适应性。H.幽门螺杆菌对人胃中ABO和刘易斯B（LeB）血型抗原的粘附是由血型抗原结合粘附素BabA介导的。大约70%的瑞典和美国。pylori临床分离株表现出Leb结合，但在这里，我们发现，babA基因存在于10个Leb非结合菌株中。荧光显微镜鉴定偶尔细菌细胞与勒布结合表型的勒布nonbincling菌株的人口。因此，非结合似乎是一种亚稳态表型。为了模拟亚稳态过渡到毒性相关的Lebing结合模式，Lebbinding克隆分离非粘附菌株通过淘选与Leb-magnetic beads和其特征。菌株17875具有两个babA基因，babA 1（沉默）和babA 2（表达）。我们发现，菌株17875的babA 2-cam衍生物通过将以前沉默的babA 1基因重组到表达的和部分同源的babB位点中来恢复Leb结合。嵌合BabB/A粘附素结合Leb的亲和力与野生型BabA粘附素相似，但其表达水平较低，并通过滑动链错配发生相位变化。使用菌株NCTC 11638获得了等效结果。我们建议，粘附素亚稳定性和异质性有助于细菌的健身和结果在一些克隆有可能定期激活和灭活的毒力适当的强度的主机响应感染。
Heterogeneity among Helicobacter pylori strains in gastric epithelial adherence is postulated to contribute to pathogen fitness in the physiologically diverse human population. H. pylori adherence to ABO and Lewis b (Leb) blood group antigens in the human stomach is mediated by the blood group antigen-binding adhesin BabA. Approximately 70% of Swedish and U.S. H. pylori clinical isolates exhibit Leb binding, but here we show that the babA gene is present in each of 10 Leb-nonbincling strains. Fluorescence microscopy identified occasional bacterial cells with a Leb-binding phenotype in populations of Leb-nonbincling strains. Thus, nonbinding seemed to be a metastable phenotype. To model metastable transition into the virulence-associated Leb-binding mode, Lebbinding clones were isolated from nonadherent strains by panning with Leb-magnetic beads and characterized. Strain 17875 has two babA genes, babA1 (silent) and babA2 (expressed). We found that a babA2-cam derivative of strain 17875 regained Leb binding by recombination of the formerly silent babA1 gene into the expressed and partially homologous babB locus. The chimeric BabB/A adhesin binds Leb with an affinity similar to that of wild-type BabA adhesin, but its expression level was lower and was subject to phase variation through slipped-strand mispairing. Equivalent results were obtained with strain NCTC11638. We propose that adhesin metastability and heterogeneity contributes to bacterial fitness and results in some clones having potential for periodic activation and deactivation of virulence appropriate for intensity of the host response to infection.