Koskiniemi Sanna, Garza-Sánchez Fernando, Sandegren Linus, Webb Julia S, Braaten Bruce A, Poole Stephen J, Andersson Dan I, Hayes Christopher S, Low David A
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, California, United States of America.
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
PLoS Genet. 2014 Mar 27;10(3):e1004255. doi: 10.1371/journal.pgen.1004255. eCollection 2014 Mar.
Clonally derived bacterial populations exhibit significant genotypic and phenotypic diversity that contribute to fitness in rapidly changing environments. Here, we show that serial passage of Salmonella enterica serovar Typhimurium LT2 (StLT2) in broth, or within a mouse host, results in selection of an evolved population that inhibits the growth of ancestral cells by direct contact. Cells within each evolved population gain the ability to express and deploy a cryptic "orphan" toxin encoded within the rearrangement hotspot (rhs) locus. The Rhs orphan toxin is encoded by a gene fragment located downstream of the "main" rhs gene in the ancestral strain StLT2. The Rhs orphan coding sequence is linked to an immunity gene, which encodes an immunity protein that specifically blocks Rhs orphan toxin activity. Expression of the Rhs orphan immunity protein protects ancestral cells from the evolved lineages, indicating that orphan toxin activity is responsible for the observed growth inhibition. Because the Rhs orphan toxin is encoded by a fragmented reading frame, it lacks translation initiation and protein export signals. We provide evidence that evolved cells undergo recombination between the main rhs gene and the rhs orphan toxin gene fragment, yielding a fusion that enables expression and delivery of the orphan toxin. In this manner, rhs locus rearrangement provides a selective advantage to a subpopulation of cells. These observations suggest that rhs genes play important roles in intra-species competition and bacterial evolution.
克隆衍生的细菌群体表现出显著的基因型和表型多样性，这有助于它们在快速变化的环境中适应。在这里，我们表明，肠炎沙门氏菌鼠伤寒血清型LT2（StLT2）在肉汤中或在小鼠宿主体内连续传代，会导致选择出一个进化群体，该群体通过直接接触抑制祖先细胞的生长。每个进化群体中的细胞获得了表达和部署重排热点（rhs）位点内编码的一种隐秘“孤儿”毒素的能力。Rhs孤儿毒素由祖先菌株StLT2中“主要”rhs基因下游的一个基因片段编码。Rhs孤儿编码序列与一个免疫基因相连，该免疫基因编码一种特异性阻断Rhs孤儿毒素活性的免疫蛋白。Rhs孤儿免疫蛋白的表达保护祖先细胞免受进化谱系的影响，表明孤儿毒素活性是观察到的生长抑制的原因。由于Rhs孤儿毒素由一个片段化的阅读框编码，它缺乏翻译起始和蛋白质输出信号。我们提供的证据表明，进化细胞在主要rhs基因和rhs孤儿毒素基因片段之间发生重组，产生一种融合体，使孤儿毒素能够表达和传递。通过这种方式，rhs位点重排为细胞亚群提供了选择优势。这些观察结果表明，rhs基因在种内竞争和细菌进化中发挥着重要作用。
