Expression of different group A streptococcal M proteins in an isogenic background demonstrates diversity in adherence to and invasion of eukaryotic cells

Expression of different group A streptococcal M proteins in an isogenic background demonstrates diversity in adherence to and invasion of eukaryotic cells
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DOI:
10.1046/j.1365-2958.1999.01289.x
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发表时间:
1999-03-01
影响因子:
3.6
通讯作者:
Hanski, E
Hanski, E
中科院分区:
生物学2区
文献类型:
--
作者:
Berkower, C;Ravins, M;Hanski, E

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A组链球菌(GAS)的M蛋白被认为是一种主要的毒力因子,因为它使GAS对吞噬作用具有抗性,并允许细菌在人血液中生长。有超过80种已知的M蛋白血清型,并且在人类疾病期间产生的保护性调理素抗体是血清型特异性的。M蛋白还介导细菌粘附于皮肤和咽部的上皮细胞。GAS菌株的mga调节子的基因组结构不同,其中包含编码M和M样蛋白以及其他毒力因子的基因。这种组织的多样性使得难以评估不同血清型的M蛋白的毒力,除非它们可以在等基因背景中表达。在此,我们在M蛋白和蛋白F1缺陷的GAS菌株SAMP中表达不同血清型的M蛋白,SAMP也缺乏M样蛋白。编码不同血清型的M蛋白(emmX)的基因已整合到SAM 2染色体中,与emm6.1启动子及其mga调节子在框内,导致类似水平的emmX表达。尽管SAMS对HEp-2和HaCaT细胞表现出非常低水平的粘附和侵入,但表达M6蛋白的SAMS衍生菌株粘附并侵入两种细胞类型。相反,表达M18蛋白的等基因菌株粘附两种细胞类型,但侵入效率非常低。表达M3蛋白的菌株粘附于两种类型的细胞,但其对HEp-2细胞的侵袭是血清依赖性的。表达M6蛋白的GAS菌株不与表达M18蛋白的同基因菌株竞争粘附或侵袭HaCaT细胞。我们的结论是,不同血清型的M蛋白识别真核细胞表面不同的受体库。
The M protein of group A streptococcus (GAS) is considered to be a major virulence factor because it renders GAS resistant to phagocytosis and allows bacterial growth in human blood. There are more than 80 known serotypes of M proteins, and protective opsonic antibodies produced during disease in humans are serotype specific. M proteins also mediate bacterial adherence to epithelial cells of skin and pharynx. GAS strains vary in the genomic organization of the mga regulon, which contains the genes encoding M and M-like proteins and other virulence factors. This diversity of organization makes it difficult to assess virulence of M proteins of different serotypes, unless they can be expressed in an isogenic background. Here, we express M proteins of different serotypes in the M protein- and protein F1-deficient GAS strain, SAMP, which also lacks M-like proteins, Genes encoding M proteins of different serotypes (emmXs) have been integrated into the SAM2 chromosome in frame with the emm6.1 promoter and its mga regulon, resulting in similar levels of emmX expression. Although SAMS exhibits a very low level of adherence to and invasion of HEp-2 and HaCaT cells, a SAMS-derived strain expressing M6 protein adheres to and invades both cell types, In contrast, the isogenic strain expressing M18 protein adheres to both cell types, but invades with a very low efficiency. A strain expressing M3 protein adheres to both types of cells, but its invasion of HEp-2 cells is serum dependent. A GAS strain expressing M6 protein does not compete with the isogenic strain expressing M18 protein for adherence to or invasion of HaCaT cells. We conclude that M proteins of different serotypes recognize different repertoires of receptors on the surfaces of eukaryotic cells.