母乳源表皮葡萄球菌比较基因组学

Comparative genomics of Staphylococcus epidermidis isolates from breast milk

摘要:

目的 表皮葡萄球菌(Staphylococcus epidermidis)是一种凝固酶阴性、革兰氏染色阳性的球菌，广泛存在于皮肤、母乳和血液等环境中。母乳中的细菌对婴幼儿肠道初始菌群的建立及免疫力的提高具有至关重要的作用，本研究通过比较基因组学分析，以期了解母乳源表皮葡萄球菌的遗传多样性和功能基因特征。方法 使用Illumina NovaSeq高通量测序平台，对前期分离自健康母乳中的110株表皮葡萄球菌进行基因组测序，并结合NCBI已公开的263株皮肤源、血液源和母乳源表皮葡萄球菌的基因组序列进行比较基因组学分析。结果 373株表皮葡萄球菌的基因组大小为(2.50±0.33) Mb，G+C含量为(32.0±0.1)%，编码序列(coding sequence, CDs)数量为(2 331±368)个。不同分离源的菌株在基因组大小和CDs数量上均存在显著差异(P<0.05)，其中血液源菌株的基因组较大且CDs数量较多。系统发育树结果显示，表皮葡萄球菌在系统发育树上呈现一定的分离源聚类趋势，体内分离源(母乳源和血液源)菌株的亲缘关系更近。不同分离源的菌株在携带毒力因子和耐药基因的数量上也存在显著差异(P<0.05)，血液源菌株携带的毒力基因和耐药基因种类最多，而母乳源菌株携带毒力基因和耐药基因种类最少。结论 表皮葡萄球菌为了适应不同生境发生了适应性进化。相较于皮肤源和血液源菌株，母乳源菌株在生物膜合成相关基因、耐药基因及毒力因子的携带率上较低。本研究为表皮葡萄球菌的适应性进化提供了新的见解，并为后续母乳源分离株遗传背景的相关研究提供了一定的理论依据。

Abstract:

Objective Staphylococcus epidermidis is a coagulase-negative, Gram-positive coccobacillus that is widely found in the skin, breast milk, and blood. Bacteria in breast milk play a crucial role in the establishment of the gut microbiota in the intestinal tract and in the enhancement of immunity of infants. We then performed comparative genomic analyses to understand the genetic diversity and functional genes of breast milk-derived S. epidermidis.Methods We used the Illumina NovaSeq platform to sequence the genomes of 110 strains of S. epidermidis preliminarily isolated from healthy breast milk by our research team. We then performed comparative genomic analyses for the 110 strains and 263 skin, blood, and breast milk-derived S. epidermidis strains publicly available from the NCBI.Results The genome size of the 373 strains of S. epidermidis was (2.50±0.33) Mb, with the G+C content was (32.0±0.1)%, and the number of coding sequences (CDs) being 2 331±368. Differences existed in genome size and number of CDs among breast, blood, and skin isolates (P<0.05), with blood isolates having the largest genome size and the highest number of CDs. The phylogenetic tree showed that the S. epidermidis isolates of the same source had obvious aggregation, and the breast milk isolates and blood isolates were more closely related. There were differences in the number of virulence factors and drug resistance genes among the strains of three sources (P<0.05). The blood-derived strains exhibited the highest diversity of virulence and resistance genes, whereas the breast milk-derived strains displayed the lowest diversity of such genes.Conclusion S. epidermidis has undergone adaptive evolution to different habitats. Compared with skin- and blood-derived strains, breast milk-derived strains carry few genes related to biofilm synthesis, drug resistance, and virulence. This study gives new insights into the adaptive evolution of S. epidermidis and provides a theoretical basis for subsequent research on the genetic background of breast milk isolates.