Ravi Keerthikka, Falkowski Nicole R, Huffnagle Gary B
Department of Molecular, Cellular & Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
mSphere. 2025 Jun 25;10(6):e0005225. doi: 10.1128/msphere.00052-25. Epub 2025 May 13.
We conducted a comparative genomic analysis of strains isolated from the gastrointestinal tract of diverse vertebrate hosts to explore the genetic basis of host specificity. We then utilized transcriptomics analysis to investigate the expression profile of identified rodent-specific genes in mouse isolate MR1 during and growth conditions. There was significant heterogeneity among strains, in both genome sequence and content, with phylogenetic clustering of strains into distinct clades associated with rodent or avian sources. There were not sufficient genomes to identify whether porcine isolates formed their own genetic clade. However, human isolates did not form a distinct clade. Functional enrichment analysis revealed significant enrichment of several genes, including surface proteins and accessory secretory pathway-related genes, as well as tyrosine decarboxylase genes in rodent isolates compared to avian isolates, including in mouse isolate MR1. A total of 40 genes were identified as rodent-associated, and all were transcriptionally active in MR1. The global transcriptomic analysis of MR1 was done using cells grown anaerobically, at 37˚C, under both the late-exponential phase and stationary phase, as well as during growth in the cecum of mono-colonized germ-free mice. Several of these genes were uniquely regulated during late exponential vs stationary phase growth and colonization in mice, highlighting their potential role in nutrient adaptation and host-microbe interactions.IMPORTANCE is a well-known probiotic species with health-beneficial properties, including host immunomodulation and pathogen inhibition. Its growing relevance in the medical industry highlights the need to understand its biology, particularly how it adapts to different host environments. In bacteria, niche adaptation is often accompanied by the loss or gain of coding sequences along with changes in the genome size. In this study, we explored the genetic diversity of strains from the gastrointestinal tracts of various vertebrates such as rodents, birds, swine, and humans. We found associations between genome content and host species of origin and could conceptually demonstrate that these genes are being differentially transcribed under varying conditions. Several functions were associated with specific host groups, suggesting that strains have adapted to their hosts over time.
我们对从不同脊椎动物宿主胃肠道分离出的菌株进行了比较基因组分析,以探索宿主特异性的遗传基础。然后,我们利用转录组学分析来研究在不同生长条件下,从小鼠分离株MR1中鉴定出的啮齿动物特异性基因的表达谱。菌株之间在基因组序列和内容上存在显著的异质性,菌株通过系统发育聚类形成与啮齿动物或鸟类来源相关的不同进化枝。没有足够的基因组来确定猪分离株是否形成了自己的遗传进化枝。然而,人类分离株并未形成一个独特的进化枝。功能富集分析显示,与鸟类分离株相比,啮齿动物分离株(包括小鼠分离株MR1)中有几个基因显著富集,包括表面蛋白和辅助分泌途径相关基因,以及酪氨酸脱羧酶基因。总共鉴定出40个与啮齿动物相关的基因,并且所有这些基因在MR1中都具有转录活性。对MR1的全局转录组分析是使用在37˚C厌氧条件下生长的细胞进行的,这些细胞处于指数后期和稳定期,以及在单定殖无菌小鼠盲肠中的生长过程中。其中一些基因在指数后期与稳定期生长以及在小鼠体内定殖过程中受到独特的调控,突出了它们在营养适应和宿主-微生物相互作用中的潜在作用。重要性是一种具有健康有益特性的著名益生菌物种,包括宿主免疫调节和病原体抑制。它在医疗行业中日益重要,这凸显了了解其生物学特性的必要性,特别是它如何适应不同的宿主环境。在细菌中,生态位适应通常伴随着编码序列的丢失或获得以及基因组大小的变化。在本研究中,我们探索了来自各种脊椎动物(如啮齿动物、鸟类、猪和人类)胃肠道的菌株的遗传多样性。我们发现了基因组内容与宿主物种起源之间的关联,并从概念上证明这些基因在不同条件下被差异转录。几种功能与特定的宿主群体相关,这表明菌株随着时间的推移已经适应了它们的宿主。