科学家发现引起胃炎、胃溃疡和胃癌的细菌有特别的、快速进化和适应不同种群的胃的能力。Marina Aspholm-Hurtig和同事提出，幽门螺旋杆菌能根据宿主胃中的环境对自身做微小的调节以适应之的能力是其在全球异常成功的原因。幽门螺旋杆菌感染了至少一半的世界人口。研究人员发现95%的世界范围幽门螺旋杆菌株附在和A、B、O血型组有关的胃抗原上。与此相比，60%的南美印地安株附在胃中与O型血有关的抗原上，O型是美印地安人的主要血型。文章作者提出，美印地安株主要是在欧洲探险者发现新大陆后的500年中从欧洲株进化而来的。这些发现也许能帮助解释美印地安人中胃溃疡发病率高的原因。
Functional Adaptation of BabA, the H. pylori ABO Blood Group Antigen Binding Adhesin
Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O–dominant human populations.
Fig. 1. (A) Structures of fucosylated blood group antigens and their relationship to the ABO system. Fuc, green; Gal, pink; GalNAc, blue (table S1). (B) ALeb inhibits adherence of H. pylori. Gastric mucosa stained with hematoxylin and eosin (i) and with Leb-mAb (arrow) (ii). Fluorescein isothiocyanate–labeled cells of strains 17875 (iii) and P466 (iv) adhere to the gastric epithelium. Pretreatment with ALeb eliminated adherence of 17875 (v) but did not affect P466 (vi). In contrast, pretreatment with Leb eliminated adherence of both 17875 (vii) and P466 (viii). Adherent bacteria were quantified in fig. S2. (C) H. pylori bound to soluble 125I-labeled blood group antigens. (D) Leb/ALeb binding ratios distinguish specialist and generalist strains. Sources of strains: SA/S and SA/G, South American specialists (48/77 = 62%) and generalists (29/77 = 38%); A, Alaska Native (24); J, Japanese (25); Sw, Swedish (76); G, German (41); S, Spanish (22). Strains tested are listed in Table 1, column I. Generalists were defined as exhibiting Leb/ALeb ratios of <2.5 (95% confidence interval). This confidence interval has its basis in consideration of Leb/ALeb binding ratios from all populations (table S4), except the South American population and one unusual Spanish specialist, strain S831 (arrow, Leb/ALeb ration > 70). Specialists stand out in this bimodal distribution as strains with Leb/ALeb rations 2.5.
Fig. 2. ML analysis of babA sequences from 66 clinical isolates showing that specialists and generalists are not phylogenetically distinct. Branches with significant bootstrap support ( 50) are indicated; origins of H. pylori strains are color coded: red, Peru; green, Spain; blue, Alaska Natives; pink, Japan; and black, Venezuelan Amazon. indicates Peruvian specialists and indicates rare specialists from other geographic regions. The A714 babA branch has been truncated about sixfold to conserve space. Bar indicates 0.1 nucleotide substitution per site.
