{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:08:48Z","timestamp":1790518128547,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009995","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000}}],"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"division of intramural research, national institute of allergy and infectious diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Yersinia murine toxin (Ymt) is a phospholipase D encoded on a plasmid acquired by <jats:italic>Yersinia pestis<\/jats:italic> after its recent divergence from a <jats:italic>Yersinia pseudotuberculosis<\/jats:italic> progenitor. Despite its name, Ymt is not required for virulence but acts to enhance bacterial survival in the flea digestive tract. Certain <jats:italic>Y<\/jats:italic>. <jats:italic>pestis<\/jats:italic> strains circulating in the Bronze Age lacked Ymt, suggesting that they were not transmitted by fleas. However, we show that the importance of Ymt varies with host blood source. In accordance with the original description, Ymt greatly enhanced <jats:italic>Y<\/jats:italic>. <jats:italic>pestis<\/jats:italic> survival in fleas infected with bacteremic mouse, human, or black rat blood. In contrast, Ymt was much less important when fleas were infected using brown rat blood. A <jats:italic>Y<\/jats:italic>. <jats:italic>pestis<\/jats:italic> Ymt<jats:sup>\u2212<\/jats:sup> mutant infected fleas nearly as well as the Ymt<jats:sup>+<\/jats:sup> parent strain after feeding on bacteremic brown rat blood, and the mutant was transmitted efficiently by flea bite during the first weeks after infection. The protective function of Ymt correlated with red blood cell digestion kinetics in the flea gut. Thus, early <jats:italic>Y<\/jats:italic>. <jats:italic>pestis<\/jats:italic> strains that lacked Ymt could have been maintained in flea-brown rat transmission cycles, and perhaps in other hosts with similar blood characteristics. Acquisition of Ymt, however, served to greatly expand the range of hosts that could support flea-borne plague.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009995","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T20:51:14Z","timestamp":1634244674000},"page":"e1009995","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":42,"title":["Acquisition of yersinia murine toxin enabled Yersinia pestis to expand the range of mammalian hosts that sustain flea-borne plague"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5052-5599","authenticated-orcid":true,"given":"David M.","family":"Bland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6251-8890","authenticated-orcid":true,"given":"Ad\u00e9la\u00efde","family":"Miarinjara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher F.","family":"Bosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1916-143X","authenticated-orcid":true,"given":"Jeanette","family":"Calarco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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Biol."},{"issue":"17","key":"ppat.1009995.ref033","doi-asserted-by":"crossref","first-page":"11824","DOI":"10.1074\/jbc.274.17.11824","article-title":"Expression, characterization, and mutagenesis of the Yersinia pestis murine toxin, a phospholipase D superfamily member","volume":"274","author":"AE Rudolph","year":"1999","journal-title":"J. Biol. Chem"},{"issue":"1","key":"ppat.1009995.ref034","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1128\/CMR.10.1.35","article-title":"Yersinia pestis\u2014etiologic agent of plague","volume":"10","author":"RD Perry","year":"1997","journal-title":"Clin. Microbiol. Rev"},{"issue":"3","key":"ppat.1009995.ref035","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1128\/iai.55.3.572-578.1987","article-title":"Resistance to pesticin, storage of iron, and invasion of HeLa cells by Yersiniae","volume":"55","author":"DJ Sikkema","year":"1987","journal-title":"Infect. 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