Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, Michigan, United States of America.
PLoS One. 2011 Jan 24;6(1):e16399. doi: 10.1371/journal.pone.0016399.
The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10(-/-) mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64 Mb genome to 200-500 X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host.
食源性病原体空肠弯曲菌的基因组包含多个高度易变的位点，或应急位点。有人认为，这些位点的固定变异是快速适应新环境的一种机制，但这一现象尚未在实验中得到证实。在之前的工作中，我们表明空肠弯曲菌 NCTC11168 的毒力在通过 C57BL/6 IL-10(-/-) 弯曲菌病小鼠模型连续传代后增加。在这里，我们试图确定在传代过程中这种适应的遗传基础。对 1.64 Mb 基因组进行 200-500 X 覆盖的重新测序，使我们能够以前所未有的深度定义 23 个应急位点在体内适应前后的变异。在适应小鼠的空肠弯曲菌中，突变主要局限于 13 个应急位点的同聚核苷酸链。这些变化导致表面结构生物合成基因座中开放阅读框和只有假定功能基因的显著改变。几个具有开放阅读框变化的基因座的转录本丰度也发生了改变。在空肠弯曲菌体内传代过程中特定应急位点的增加，加上观察到的毒力增加和缺乏其他类型的遗传变化，是这些可变区域在空肠弯曲菌适应新宿主的毒力中发挥重要作用的第一个实验证据。
