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全基因组分析无乳链球菌在人全血和血浆中存活所需的基因。

Genome-Wide Assessment of Streptococcus agalactiae Genes Required for Survival in Human Whole Blood and Plasma.

机构信息

Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA

Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.

出版信息

Infect Immun. 2020 Sep 18;88(10). doi: 10.1128/IAI.00357-20.

Abstract

(group B streptococcus, or GBS) is a common cause of bacteremia and sepsis in newborns, pregnant women, and immunocompromised patients. The molecular mechanisms used by GBS to survive and proliferate in blood are not well understood. Here, using a highly virulent GBS strain and transposon-directed insertion site sequencing (TraDIS), we performed genome-wide screens to discover novel GBS genes required for bacterial survival in human whole blood and plasma. The screen identified 85 and 41 genes that are required for GBS growth in whole blood and plasma, respectively. A common set of 29 genes was required in both whole blood and plasma. Targeted gene deletion confirmed that (i) genes encoding methionine transporter () and manganese transporter () are crucial for GBS survival in whole blood and plasma, (ii) gene W903_1820, encoding a small multidrug export family protein, contributes significantly to GBS survival in whole blood, (iii) the shikimate pathway gene is essential for GBS growth in whole blood and plasma, and (iv) deletion of , encoding a fibrinogen-binding adhesin, increases GBS survival in whole blood. Our findings provide new insight into the GBS-host interactions in human blood.

摘要

(GBS)是导致新生儿、孕妇和免疫功能低下患者菌血症和败血症的常见原因。GBS 在血液中存活和增殖所使用的分子机制还不是很清楚。在这里,我们使用一种高毒力的 GBS 菌株和转座子定向插入位点测序(TraDIS),进行了全基因组筛选,以发现新型 GBS 基因,这些基因对于 GBS 在人全血和血浆中的存活是必需的。该筛选鉴定出了 85 个和 41 个分别在全血和血浆中生长所必需的基因。一组共同的 29 个基因在全血和血浆中都是必需的。靶向基因缺失证实了(i)编码甲硫氨酸转运体()和锰转运体()的基因对于 GBS 在全血和血浆中的存活至关重要,(ii)编码小多药外排家族蛋白的基因 W903_1820 对 GBS 在全血中的存活有重要贡献,(iii)莽草酸途径基因 对于 GBS 在全血和血浆中的生长是必需的,以及(iv)缺失编码纤维蛋白原结合黏附素的基因 会增加 GBS 在全血中的存活。我们的发现为 GBS 在人血液中的宿主相互作用提供了新的见解。

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