Selection of Staphylococcus aureus in a murine nasopharyngeal colonization model.
Selection of Staphylococcus aureus in a murine nasopharyngeal colonization model.
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DOI：
10.3389/fcimb.2022.874138
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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金黄色葡萄球菌鼻腔定植是感染的危险因素。很大一部分人口被确定为潜在的S。金黄色葡萄球菌携带者，但我们只部分了解的遗传因素，促进长期鼻腔定植的剧目。在这里，我们提出了一个小鼠模型的鼻咽定植，需要低S。金黄色葡萄球菌接种物，并服从实验进化方法。我们使用这个模型来实验性地进化S。金黄色葡萄球菌使用鼻咽中的连续传代来鉴定那些选择下的遗传基因座。在3个周期的定植后，在甘露醇、山梨醇、精氨酸、亚硝酸盐和乳酸盐代谢基因中鉴定了促进鼻定植关键途径的突变。应激反应被确定为处于选择压力下，DNA修复基因包括dnaJ和recF以及关键应激反应基因clpL、rpoB和ahpF发生突变。肽聚糖合成途径基因也揭示了突变，表明细胞表面改变的潜在选择。这里使用的小鼠模型是通用的问题殖民化，持久性和进化研究。我们研究了人类病原体金黄色葡萄球菌，以确定有助于其在人类鼻子和喉咙中生存的因素。前鼻孔和鼻咽被认为是主要的栖息地，但我们不知道病原体如何适应，因为它从一个人到另一个人。我们首先确定了病原体在鼻咽中持续存活多天，这可能是人类持久性的良好模型，因为它建立所需的细菌数量很少。通过在不同小鼠的鼻咽部进行连续几轮的定殖，我们揭示了S。金黄色葡萄球菌发生。这些变化是在与细胞表面和代谢相关的基因中发现的，可能表明对生态位的适应。一个基因显示出多个突变的积累，支持适应的关键贡献，但它编码的蛋白质的作用尚不清楚。这些基因和遗传变化的贡献尚不清楚，但表明未来研究的一个领域，以更好地了解这种常见的人类病原体如何在人类殖民和生存方面如此成功。
Staphylococcus aureus nasal colonization is a risk factor for infection. A large proportion of the population are identified as potential S. aureus carriers yet we only partially understand the repertoire of genetic factors that promote long-term nasal colonization. Here we present a murine model of nasopharyngeal colonization that requires a low S. aureus inoculum and is amenable to experimental evolution approaches. We used this model to experimentally evolve S. aureus using successive passages in the nasopharynx to identify those genetic loci under selection. After 3 cycles of colonization, mutations were identified in mannitol, sorbitol, arginine, nitrite and lactate metabolism genes promoting key pathways in nasal colonization. Stress responses were identified as being under selective pressure, with mutations in DNA repair genes including dnaJ and recF and key stress response genes clpL, rpoB and ahpF. Peptidoglycan synthesis pathway genes also revealed mutations indicating potential selection for alteration of the cell surface. The murine model used here is versatile to question colonization, persistence and evolution studies. We studied the human pathogen Staphylococcus aureus in our search to determine factors that contribute to its ability to live in the human nose and throat. The anterior nares and nasopharynx are considered primary habitats but we do not understand how the pathogen adapts as it moves from one person to the next. We first determined sustained survival of the pathogen over multiple days in the nasopharynx that might act as a good model for human persistence due to the low numbers of bacteria needed for it to establish. By using successive rounds of colonization of the nasopharynx across different mice we revealed that multiple genetic changes in the S. aureus occurred. These changes were found in genes associated with the cell surface and metabolism and might indicate adaptation to the niche. One gene showed an accumulation of multiple mutations supporting a key contribution in adaptation but the role of the protein it encodes is not yet known. The contribution of these genes and genetic changes are unclear but indicate an area for future research to better understand how this common human pathogen is so successful at human colonization and survival.
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影响因子：
6.7
作者：
Baur S;Rautenberg M;Faulstich M;Grau T;Severin Y;Unger C;Hoffmann WH;Rudel T;Autenrieth IB;Weidenmaier C
通讯作者：
Weidenmaier C
影响因子：
4.2
作者：
Corrigan, Rebecca M.;Miajlovic, Helen;Foster, Timothy J.
通讯作者：
Foster, Timothy J.
影响因子：
6.4
作者：
Diep, Binh An;Stone, Gregory G.;Chambers, Henry F.
通讯作者：
Chambers, Henry F.
影响因子：
6.4
作者：
Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW
影响因子：
4.5
作者：
Khemici, Vanessa;Prados, Julien;Redder, Peter
通讯作者：
Redder, Peter