期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：3
页码：863-868
DOI：10.1073/pnas.1416707112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceCommon features have been observed in the genome sequences of bacterial pathogens that infect few hosts. These "host adaptations" include the acquisition of pathogenicity islands of multiple genes involved in disease, losses of whole genes, and even single mutations that affect gene function. Within Salmonella enterica is a natural model system of four pathogens that are each other's closest relatives, including a host-generalist, two host-specialists, and one with strong host associations. With whole-genome sequences, we aimed to improve our understanding of the number, nature, and order of these host adaptation events, shedding light on how human and animal pathogens arose in the past, and potentially allowing us to predict how emerging pathogens will evolve in the future. Many bacterial pathogens are specialized, infecting one or few hosts, and this is often associated with more acute disease presentation. Specific genomes show markers of this specialization, which often reflect a balance between gene acquisition and functional gene loss. Within Salmonella enterica subspecies enterica, a single lineage exists that includes human and animal pathogens adapted to cause infection in different hosts, including S. enterica serovar Enteritidis (multiple hosts), S. Gallinarum (birds), and S. Dublin (cattle). This provides an excellent evolutionary context in which differences between these pathogen genomes can be related to host range. Genome sequences were obtained from [~]60 isolates selected to represent the known diversity of this lineage. Examination and comparison of the clades within the phylogeny of this lineage revealed signs of host restriction as well as evolutionary events that mark a path to host generalism. We have identified the nature and order of events for both evolutionary trajectories. The impact of functional gene loss was predicted based upon position within metabolic pathways and confirmed with phenotyping assays. The structure of S. Enteritidis is more complex than previously known, as a second clade of S. Enteritidis was revealed that is distinct from those commonly seen to cause disease in humans or animals, and that is more closely related to S. Gallinarum. Isolates from this second clade were tested in a chick model of infection and exhibited a reduced colonization phenotype, which we postulate represents an intermediate stage in pathogen-host adaptation.
