{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:53:22Z","timestamp":1791248002333,"version":"4.1.0"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T00:00:00Z","timestamp":1408406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T00:00:00Z","timestamp":1409270400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,8,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Rapid growth in deep tissue is essential to the high virulence of\n            <jats:named-content content-type=\"genus-species\">Yersinia pestis<\/jats:named-content>\n            , causative agent of plague. To better understand the mechanisms underlying this unusual ability, we used transposon mutagenesis and high-throughput sequencing (Tn-seq) to systematically probe the\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            genome for elements contributing to fitness during infection. More than a million independent insertion mutants representing nearly 200,000 unique genotypes were generated in fully virulent\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            . Each mutant in the library was assayed for its ability to proliferate\n            <jats:italic>in vitro<\/jats:italic>\n            on rich medium and in mice following intravenous injection. Virtually all genes previously established to contribute to virulence following intravenous infection showed significant fitness defects, with the exception of genes for yersiniabactin biosynthesis, which were masked by strong intercellular complementation effects. We also identified more than 30 genes with roles in nutrient acquisition and metabolism as experiencing strong selection during infection. Many of these genes had not previously been implicated in\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            virulence. We further examined the fitness defects of strains carrying mutations in two such genes\u2014encoding a branched-chain amino acid importer (\n            <jats:italic>brnQ<\/jats:italic>\n            ) and a glucose importer (\n            <jats:italic>ptsG<\/jats:italic>\n            )\u2014both\n            <jats:italic>in vivo<\/jats:italic>\n            and in a novel defined synthetic growth medium with nutrient concentrations matching those in serum. Our findings suggest that diverse nutrient limitations in deep tissue play a more important role in controlling bacterial infection than has heretofore been appreciated. Because much is known about\n            <jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>\n            pathogenesis, this study also serves as a test case that assesses the ability of Tn-seq to detect virulence genes.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Our understanding of the functions required by bacteria to grow in deep tissues is limited, in part because most growth studies of pathogenic bacteria are conducted on laboratory media that do not reflect conditions prevailing in infected animal tissues. Improving our knowledge of this aspect of bacterial biology is important as a potential pathway to the development of novel therapeutics.\n            <jats:named-content content-type=\"genus-species\">Yersinia pestis<\/jats:named-content>\n            , the plague bacterium, is highly virulent due to its rapid dissemination and growth in deep tissues, making it a good model for discovering bacterial adaptations that promote rapid growth during infection. Using Tn-seq, a genome-wide fitness profiling technique, we identified several functions required for fitness of\n            <jats:italic>Y.\u00a0pestis in vivo<\/jats:italic>\n            that were not previously known to be important. Most of these functions are needed to acquire or synthesize nutrients. Interference with these critical nutrient acquisition pathways may be an effective strategy for designing novel antibiotics and vaccines.\n          <\/jats:p>","DOI":"10.1128\/mbio.01385-14","type":"journal-article","created":{"date-parts":[[2014,8,20]],"date-time":"2014-08-20T04:58:45Z","timestamp":1408510725000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":68,"title":["Genome-Wide Mutant Fitness Profiling Identifies Nutritional Requirements for Optimal Growth of Yersinia pestis in Deep Tissue"],"prefix":"10.1128","volume":"5","author":[{"given":"Samantha G.","family":"Palace","sequence":"first","affiliation":[{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan K.","family":"Proulx","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon D.","family":"Goguen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.77.3.317-321.1959"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06341.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-139-9-2159"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.5.1659-1668.1997"},{"key":"e_1_3_2_6_2","first-page":"570","article-title":"The pigmentation of Pasteurella pestis on a defined medium containing haemin","volume":"37","author":"Burrows TW","year":"1956","unstructured":"BurrowsTW JacksonS . 1956. 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