{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T10:23:39Z","timestamp":1792923819958,"version":"4.5.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,3,31]]},"abstract":"<jats:p>\n                    Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example,\n                    <jats:italic>Shigella<\/jats:italic>\n                    spp., the causative agents of bacillary dysentery, differ from the closely related commensal\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    in the presence of a plasmid in\n                    <jats:italic>Shigella<\/jats:italic>\n                    that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in \u224890% of\n                    <jats:italic>E. coli<\/jats:italic>\n                    strains but is uniformly absent in\n                    <jats:italic>Shigella<\/jats:italic>\n                    strains. When the gene for LDC,\n                    <jats:italic>cadA<\/jats:italic>\n                    , was introduced into\n                    <jats:italic>Shigella flexneri<\/jats:italic>\n                    2a, virulence became attenuated, and enterotoxin activity was inhibited greatly. The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC. Comparison of the\n                    <jats:italic>S. flexneri<\/jats:italic>\n                    2a and laboratory\n                    <jats:italic>E. coli<\/jats:italic>\n                    K-12 genomes in the region of\n                    <jats:italic>cadA<\/jats:italic>\n                    revealed a large deletion in\n                    <jats:italic>Shigella<\/jats:italic>\n                    . Representative strains of\n                    <jats:italic>Shigella<\/jats:italic>\n                    spp. and enteroinvasive\n                    <jats:italic>E. coli<\/jats:italic>\n                    displayed similar deletions of\n                    <jats:italic>cadA<\/jats:italic>\n                    . Our results suggest that, as\n                    <jats:italic>Shigella<\/jats:italic>\n                    spp. evolved from\n                    <jats:italic>E. coli<\/jats:italic>\n                    to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions. The formation of these \u201cblack holes,\u201d deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence. Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy. Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.7.3943","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"3943-3948","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":377,"title":["\u201cBlack holes\u201d and bacterial pathogenicity: A large genomic deletion that enhances the virulence of\n                    <i>Shigella<\/i>\n                    spp. and enteroinvasive\n                    <i>Escherichia coli<\/i>"],"prefix":"10.1073","volume":"95","author":[{"given":"Anthony T.","family":"Maurelli","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, F. Edward H\u00e9bert School of Medicine, Bethesda, MD 20814-4799; Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI 48109-0656; and Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201-1595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinaldo E.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, F. Edward H\u00e9bert School of Medicine, Bethesda, MD 20814-4799; Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI 48109-0656; and Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201-1595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Bloch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, F. Edward H\u00e9bert School of Medicine, Bethesda, MD 20814-4799; Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI 48109-0656; and Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201-1595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Rode","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, F. Edward H\u00e9bert School of Medicine, Bethesda, MD 20814-4799; Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI 48109-0656; and Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201-1595"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, F. 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