Shak Joshua R, Dick Jonathan J, Meinersmann Richard J, Perez-Perez Guillermo I, Blaser Martin J
Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
J Bacteriol. 2009 Nov;191(22):6900-10. doi: 10.1128/JB.00706-09. Epub 2009 Sep 11.
The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3' region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host.
幽门螺杆菌能够在人类胃部持续存在数十年而不引发杀菌免疫，这一特性令人瞩目。由于重复DNA可通过增加重组、插入和缺失来促进适应性基因组灵活性，我们在两种幽门螺杆菌菌株的基因组中搜索核苷酸重复序列。我们发现了一个具有广泛重复DNA的基因家族，我们将其命名为幽门螺杆菌RD基因家族。该家族的每个基因都由一个保守的3'区域、一个编码7个和11个氨基酸重复序列的可变中间区域以及一个包含两种可能等位基因之一的5'区域组成。对五个完整基因组序列的分析以及对42株幽门螺杆菌菌株的PCR基因分型显示，不同菌株之间RD基因在数量、位置和排列上存在广泛差异。此外，对从单个个体胃部分离出的多个菌株的检测揭示了宿主内重复序列数量和组成的差异。尽管先前有证据表明该基因家族的蛋白质产物在细菌细胞表面表达，但酶联免疫吸附测定和免疫印迹研究表明，幽门螺杆菌阳性宿主对重组RD蛋白没有一致的血清反应性。在RD基因家族中发现的重复模式似乎反映了滑链错配或结构域重复，从而在基因型和表型上实现冗余和随后的多样性。这个具有保守、重复和等位结构域的新型高变基因家族可能是理解幽门螺杆菌在其自然宿主中持续存在的一个重要位点。
