Genomic Stability and Genetic Defense Systems in Dolosigranulum pigrum, a Candidate Beneficial Bacterium from the Human Microbiome.
Genomic Stability and Genetic Defense Systems in Dolosigranulum pigrum, a Candidate Beneficial Bacterium from the Human Microbiome.
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DOI：
10.1128/msystems.00425-21
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发表时间：
2021-10-26
期刊：
影响因子：
6.4
通讯作者：
Lemon KP
中科院分区：
文献类型：
--
作者：
Flores Ramos S;Brugger SD;Escapa IF;Skeete CA;Cotton SL;Eslami SM;Gao W;Bomar L;Tran TH;Jones DS;Minot S;Roberts RJ;Johnston CD;Lemon KP
在人类鼻腔微生物群的多项流行病学研究中，色素微囊与健康指标呈正相关。了解猪瘟的基本生物学知识是评估其未来治疗应用潜力的先决条件；然而，这些数据非常有限。为了深入了解黑胶霉的染色体结构、泛基因组和基因组稳定性，我们比较了20年来收集的28个黑胶霉菌株的基因组。系统基因组学分析显示，在这一时期有密切相关的菌株流传，19个基因组的闭合显示出高度保守的染色体合性。与核心基因组相比，辅助基因组中参与移动组和防御移动遗传元件（MGEs）的基因簇富集。通过系统的MGEs分析，鉴定出了首个候选蛋白原噬菌体及其插入序列。一项对限制MGEs传播的遗传元件的系统分析，包括限制性修饰（RM）、CRISPR-Cas和神命名的防御系统，揭示了宿主防御系统的品系水平多样性，这些防御系统定位于特定的基因组位点，包括一个RM系统热点。对CRISPR间隔序列的分析指出了大量的转基因基因，而这些转基因基因是藜属植物自我防御的。这些结果揭示了水平基因转移和移动遗传元件在菌株多样化中的作用，同时强调了在pigrum中，这发生在受各种防御机制保护的高度稳定的染色体组织的背景下。重要性：大黑穗病菌是一种候选有益细菌，具有潜在的未来治疗用途。这是基于在人类一生中对人类鼻腔微生物群进行的多项研究表明，它与健康特征呈正相关。例如，在成人中，高水平的葡萄球菌鼻腔定植预示着金黄色葡萄球菌鼻腔定植的缺失。此外，在中耳感染的研究中，在幼儿中pigrum鼻定植与健康对照组相关。我们对28个基因组的分析显示，在20年的时间里，在美国人身上定殖的猪瘟杆菌菌株具有显著的稳定性。我们随后确定了影响这种稳定性的因素，包括基因组稳定性、噬菌体捕食者、MGEs在菌株水平变异中的作用以及对MGEs的防御。最后，这些pigrum菌株也缺乏预测的毒力因子。总的来说，这些发现进一步支持了pigrum作为一种治疗性细菌的潜力。
Dolosigranulum pigrum is positively associated with indicators of health in multiple epidemiological studies of human nasal microbiota. Knowledge of the basic biology of D. pigrum is a prerequisite for evaluating its potential for future therapeutic use; however, such data are very limited. To gain insight into D. pigrum’s chromosomal structure, pangenome, and genomic stability, we compared the genomes of 28 D. pigrum strains that were collected across 20 years. Phylogenomic analysis showed closely related strains circulating over this period and closure of 19 genomes revealed highly conserved chromosomal synteny. Gene clusters involved in the mobilome and in defense against mobile genetic elements (MGEs) were enriched in the accessory genome versus the core genome. A systematic analysis for MGEs identified the first candidate D. pigrum prophage and insertion sequence. A systematic analysis for genetic elements that limit the spread of MGEs, including restriction modification (RM), CRISPR-Cas, and deity-named defense systems, revealed strain-level diversity in host defense systems that localized to specific genomic sites, including one RM system hot spot. Analysis of CRISPR spacers pointed to a wealth of MGEs against which D. pigrum defends itself. These results reveal a role for horizontal gene transfer and mobile genetic elements in strain diversification while highlighting that in D. pigrum this occurs within the context of a highly stable chromosomal organization protected by a variety of defense mechanisms. IMPORTANCE Dolosigranulum pigrum is a candidate beneficial bacterium with potential for future therapeutic use. This is based on its positive associations with characteristics of health in multiple studies of human nasal microbiota across the span of human life. For example, high levels of D. pigrum nasal colonization in adults predicts the absence of Staphylococcus aureus nasal colonization. Also, D. pigrum nasal colonization in young children is associated with healthy control groups in studies of middle ear infections. Our analysis of 28 genomes revealed a remarkable stability of D. pigrum strains colonizing people in the United States across a 20-year span. We subsequently identified factors that can influence this stability, including genomic stability, phage predators, the role of MGEs in strain-level variation, and defenses against MGEs. Finally, these D. pigrum strains also lacked predicted virulence factors. Overall, these findings add additional support to the potential for D. pigrum as a therapeutic bacterium.