科學(xué)家發(fā)現(xiàn)引起胃炎,、胃潰瘍和胃癌的細菌有特別的,、快速進化和適應(yīng)不同種群的胃的能力。Marina Aspholm-Hurtig和同事提出,，幽門螺旋桿菌能根據(jù)宿主胃中的環(huán)境對自身做微小的調(diào)節(jié)以適應(yīng)之的能力是其在全球異常成功的原因,。幽門螺旋桿菌感染了至少一半的世界人口。研究人員發(fā)現(xiàn)95%的世界范圍幽門螺旋桿菌株附在和A,、B,、O血型組有關(guān)的胃抗原上。與此相比,，60%的南美印地安株附在胃中與O型血有關(guān)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歐洲探險者發(fā)現(xiàn)新大陸后的500年中從歐洲株進化而來的,。這些發(fā)現(xiàn)也許能幫助解釋美印地安人中胃潰瘍發(fā)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.
