Mining Virulence Genes Using Metagenomics

When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.当将细菌基因组（bacterial genome）与其所栖息环境的宏基因组（metagenome）进行比对时，绝大多数基因会以较高的序列一致性（sequence identity）被宏基因组招募。针对自由生活的细菌（例如将海洋细菌与海洋宏基因组进行比对），其部分基因组区域在招募图谱中完全缺失，这意味着这些区域的基因仅存在于单个细菌分离株中。我们将这类区域称为宏基因组岛（Metagenomic Islands, MIs），研究发现，尽管人体相关环境（如肠道）存在分隔化结构，但当将人体宿主内共生细菌的基因组与人类微生物组（human microbiome）的序列进行比对时，这类宏基因组岛同样可被观测到。从应用视角出发，人类致病菌的宏基因组岛（例如在肠出血性大肠埃希菌与肠道宏基因组（gut metagenome）比对中鉴定出的岛，或是致病型脑膜炎奈瑟菌与口腔宏基因组（oral metagenome）比对中鉴定出的岛）包含了毒力基因（virulence genes），而这些毒力基因在健康个体微生物组中存在的相关菌株或物种中似乎并不存在。我们提出，该策略（即针对健康个体的宏基因组开展致病菌的比对招募分析）可用于检测那些毒力相关基因尚未得到充分解析的物种的致病区域（pathogenicity regions）。利用该方法，我们在多种人类致病菌中检测到了已知的致病岛（pathogenicity islands），并鉴定出了新的潜在毒力基因。