Department of Veterinary Disease Biology, University of Copenhagen Frederiksberg, Denmark.
Front Cell Infect Microbiol. 2012 Feb 20;2:11. doi: 10.3389/fcimb.2012.00011. eCollection 2012.
Bacteriophages are estimated to be the most abundant entities on earth and can be found in every niche where their bacterial hosts reside. The initial interaction between phages and Campylobacter jejuni, a common colonizer of poultry intestines and a major source of foodborne bacterial gastroenteritis in humans, is not well understood. Recently, we isolated and characterized a phage F336 resistant variant of C. jejuni NCTC11168 called 11168R. Comparisons of 11168R with the wildtype lead to the identification of a novel phage receptor, the phase variable O-methyl phosphoramidate (MeOPN) moiety of the C. jejuni capsular polysaccharide (CPS). In this study we demonstrate that the 11168R strain has gained cross-resistance to four other phages in our collection (F198, F287, F303, and F326). The reduced plaquing efficiencies suggested that MeOPN is recognized as a receptor by several phages infecting C. jejuni. To further explore the role of CPS modifications in C. jejuni phage recognition and infectivity, we tested the ability of F198, F287, F303, F326, and F336 to infect different CPS variants of NCTC11168, including defined CPS mutants. These strains were characterized by high-resolution magic angle spinning NMR spectroscopy. We found that in addition to MeOPN, the phase variable 3-O-Me and 6-O-Me groups of the NCTC11168 CPS structure may influence the plaquing efficiencies of the phages. Furthermore, co-infection of chickens with both C. jejuni NCTC11168 and phage F336 resulted in selection of resistant C. jejuni bacteria, which either lack MeOPN or gain 6-O-Me groups on their surface, demonstrating that resistance can be acquired in vivo. In summary, we have shown that phase variable CPS structures modulate phage infectivity in C. jejuni and suggest that the constant phage predation in the avian gut selects for changes in these structures leading to a continuing phage-host co-evolution.
噬菌体估计是地球上最丰富的实体,可以在其细菌宿主存在的每个生态位中找到。噬菌体与空肠弯曲菌(一种常见的家禽肠道定植菌,也是人类食源性细菌性胃肠炎的主要来源)之间的最初相互作用尚未得到很好的理解。最近,我们分离并鉴定了一株对噬菌体 F336 具有抗性的空肠弯曲菌 NCTC11168 变异株,称为 11168R。与野生型的比较导致了一种新型噬菌体受体的鉴定,即空肠弯曲菌荚膜多糖(CPS)的相位可变 O-甲基膦酸酯(MeOPN)部分。在这项研究中,我们证明 11168R 菌株对我们收集的其他四种噬菌体(F198、F287、F303 和 F326)具有交叉抗性。较低的噬菌斑效率表明,MeOPN 被几种感染空肠弯曲菌的噬菌体识别为受体。为了进一步探索 CPS 修饰在空肠弯曲菌噬菌体识别和感染性中的作用,我们测试了 F198、F287、F303、F326 和 F336 感染 NCTC11168 不同 CPS 变体的能力,包括定义的 CPS 突变体。这些菌株通过高分辨率魔角旋转 NMR 光谱进行了表征。我们发现,除了 MeOPN 之外,NCTC11168 CPS 结构的相位可变 3-O-Me 和 6-O-Me 基团也可能影响噬菌体的噬菌斑效率。此外,鸡的空肠弯曲菌 NCTC11168 和噬菌体 F336 的共同感染导致了对耐药空肠弯曲菌的选择,这些细菌要么缺乏 MeOPN,要么在其表面获得 6-O-Me 基团,这表明耐药性可以在体内获得。总之,我们已经表明,相位可变的 CPS 结构调节空肠弯曲菌中的噬菌体感染性,并表明禽类肠道中持续的噬菌体捕食选择了这些结构的变化,导致噬菌体-宿主的持续共同进化。