Beckett Amber C, Loh John T, Chopra Abha, Leary Shay, Lin Aung Soe, McDonnell Wyatt J, Dixon Beverly R E A, Noto Jennifer M, Israel Dawn A, Peek Richard M, Mallal Simon, Algood Holly M Scott, Cover Timothy L
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States of America.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States of America.
PeerJ. 2018 May 18;6:e4803. doi: 10.7717/peerj.4803. eCollection 2018.
requires genetic agility to infect new hosts and establish long-term colonization of changing gastric environments. In this study, we analyzed genetic adaptation in the Mongolian gerbil model. This model is of particular interest because -infected gerbils develop a high level of gastric inflammation and often develop gastric adenocarcinoma or gastric ulceration. We analyzed the whole genome sequences of strains cultured from experimentally infected gerbils, in comparison to the genome sequence of the input strain. The mean annualized single nucleotide polymorphism (SNP) rate per site was 1.5e, which is similar to the rates detected previously in infected humans. Many of the mutations occurred within or upstream of genes associated with iron-related functions (, , , , and ) or encoding outer membrane proteins ( and ). Most of the SNPs within coding regions (86%) were non-synonymous mutations. Several deletion or insertion mutations led to disruption of open reading frames, suggesting that the corresponding gene products are not required or are deleterious during chronic colonization of the gerbil stomach. Five variants (three SNPs and two deletions) were detected in isolates from multiple animals, which suggests that these mutations conferred a selective advantage. One of the mutations (FurR88H) detected in isolates from multiple animals was previously shown to confer increased resistance to oxidative stress, and we now show that this SNP also confers a survival advantage when is co-cultured with neutrophils. Collectively, these analyses allow the identification of mutations that are positively selected during colonization of the gerbil model.
需要基因灵活性来感染新宿主并在不断变化的胃部环境中建立长期定植。在本研究中，我们分析了蒙古沙鼠模型中的基因适应性。该模型特别受关注，因为感染的沙鼠会出现高水平的胃部炎症，并且经常发展为胃腺癌或胃溃疡。我们分析了从实验感染的沙鼠中培养的菌株的全基因组序列，并与输入菌株的基因组序列进行比较。每个位点的年均单核苷酸多态性（SNP）率为1.5e，这与之前在感染人类中检测到的率相似。许多突变发生在与铁相关功能相关的基因内部或上游（……）或编码外膜蛋白的基因（……）。编码区域内的大多数SNP（86%）是非同义突变。几个缺失或插入突变导致开放阅读框的破坏，这表明在沙鼠胃部的慢性定植过程中，相应的基因产物不需要或具有有害性。在来自多只动物的分离株中检测到五个变体（三个SNP和两个缺失），这表明这些突变赋予了选择性优势。在来自多只动物的分离株中检测到的一个突变（FurR88H）先前已被证明可增强对氧化应激的抗性，并且我们现在表明，当与中性粒细胞共培养时，这个SNP也赋予了生存优势。总的来说，这些分析使得能够鉴定在沙鼠模型定植过程中被正向选择的突变。
