{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:47:54Z","timestamp":1790858874828,"version":"4.1.0"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"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":[[2025,5,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The F1 protein capsule of\n              <jats:italic toggle=\"yes\">Yersinia pestis<\/jats:italic>\n              is encoded by the\n              <jats:italic toggle=\"yes\">caf<\/jats:italic>\n              operon on the 100 kb plasmid pFra and is produced at high levels in the mammalian host. Although the F1 capsule is not an essential virulence factor in many mammals,\n              <jats:italic toggle=\"yes\">Y. pestis<\/jats:italic>\n              isolates lacking the\n              <jats:italic toggle=\"yes\">caf<\/jats:italic>\n              operon are very rare in nature, indicating an essential biological role. Here, we show that F1-negative \u0394\n              <jats:italic toggle=\"yes\">caf<\/jats:italic>\n              mutants of\n              <jats:italic toggle=\"yes\">Y. pestis<\/jats:italic>\n              are virulent in a mouse model but with a longer time to terminal disease. Bacterial loads in the spleen at the terminal stage of plague were not significantly different from the wild type. However, the level of bacteremia reached by the \u0394\n              <jats:italic toggle=\"yes\">caf<\/jats:italic>\n              mutants was often significantly lower than the wild type. Fleas that fed on moribund mice infected with the \u0394\n              <jats:italic toggle=\"yes\">caf<\/jats:italic>\n              mutants ingested the expected number of bacteria, but most mice had levels of bacteremia too low to support the development of a transmissible infection in the flea. A complemented \u0394\n              <jats:italic toggle=\"yes\">caf<\/jats:italic>\n              mutant restored wildtype levels of bacteremia and median time to death. F1-negative\n              <jats:italic toggle=\"yes\">Y. pestis<\/jats:italic>\n              have a more pronounced autoaggregative phenotype, both\n              <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n              , which likely leads to a higher degree of sequestration in the spleen and other tissues. Therefore, an important biological role of the F1 capsule may be to enable\n              <jats:italic toggle=\"yes\">Y. pestis<\/jats:italic>\n              to achieve bacteremia levels high enough to efficiently infect fleas, thereby enhancing stable flea-borne transmission cycles of\n              <jats:italic toggle=\"yes\">Y. pestis<\/jats:italic>\n              .\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Arthropod-borne pathogens face two fundamental challenges in completing their life cycle\u2014they must produce a transmissible infection in both their mammalian and arthropod hosts. In order to effectively infect its flea vector,\n                <jats:italic toggle=\"yes\">Yersinia pestis<\/jats:italic>\n                , the bacterial agent of plague, must generate a high-density bacteremia in the mammalian hosts that the fleas feed upon. In this study, we found that the F1 protein capsule of\n                <jats:italic toggle=\"yes\">Y. pestis<\/jats:italic>\n                enhances the production of high bacteremia at the terminal stage of plague in a mouse model, thereby promoting successful mammal-to-flea transmission. Acquisition of the plasmid that encodes the F1 capsule occurred early in the evolutionary divergence of\n                <jats:italic toggle=\"yes\">Y. pestis<\/jats:italic>\n                from\n                <jats:italic toggle=\"yes\">Yersinia pseudotuberculosis<\/jats:italic>\n                and was likely to have been a key step in the transition to a flea-borne lifestyle.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00301-25","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T14:24:41Z","timestamp":1742999081000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Evidence of a role for the F1 capsule of\n            <i>Yersinia pestis<\/i>\n            in enhancing transmission from mammals to fleas in a mouse model of bubonic plague"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5187-8299","authenticated-orcid":true,"given":"Christopher F.","family":"Bosio","sequence":"first","affiliation":[{"name":"Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH","place":["Hamilton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton O.","family":"Jarrett","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH","place":["Hamilton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6240-7936","authenticated-orcid":true,"given":"B. Joseph","family":"Hinnebusch","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH","place":["Hamilton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.68.2.131"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00075.x"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(90)80852-a"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)80945-y"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)80331-a"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)80650-6"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.12.5731-5742.1998"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.15.3.972-977.1977"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1990.43.389"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.67.4.438-449.1954"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.6.2180-2187.1996"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0035-9203(98)90923-3"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.3.1453-1460.2002"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00612-06"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010447"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00878-d"},{"key":"e_1_3_5_18_2","first-page":"156","article-title":"Pathology of experimental pneumonic plague produced by fraction 1-positive and fraction 1-negative Yersinia pestis in African green monkeys (Cercopithecus aethiops)","volume":"120","author":"Davis KJ","year":"1996","unstructured":"Davis KJ, Fritz DL, Pitt ML, Welkos SL, Worsham PL, Friedlander AM. 1996. Pathology of experimental pneumonic plague produced by fraction 1-positive and fraction 1-negative Yersinia pestis in African green monkeys (Cercopithecus aethiops). Arch Pathol Lab Med 120:156\u2013163.","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-42-4-264"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/21.supplement_2.s178"},{"key":"e_1_3_5_21_2","first-page":"299","article-title":"Studies on the contribution of the F1 capsule-associated plasmid pFra to the virulence of Yersinia pestis","volume":"13","author":"Welkos SL","year":"1995","unstructured":"Welkos SL, Davis KM, Pitt LM, Worsham PL, Freidlander AM. 1995. Studies on the contribution of the F1 capsule-associated plasmid pFra to the virulence of Yersinia pestis. Contrib Microbiol Immunol 13:299\u2013305.","journal-title":"Contrib Microbiol Immunol"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/1791246a0"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/109.2.154"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plasmid.2003.09.003"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01949752"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00981-10"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00950-08"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.87.1.64"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00718-09"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.12.4310-4317.1991"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019267"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003196"},{"key":"e_1_3_5_33_2","unstructured":"Bland DM Brown LD Jarrett CO Hinnebusch BJ Macaluso KR. 2017. BEI Resources. Methods in flea research. Available from: https:\/\/www.beiresources.org\/Portals\/2\/Methods%20in%20Flea%20Research%20v2.pdf"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009995"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00997-09"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1086\/429931"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2000.62.552"},{"key":"e_1_3_5_38_2","first-page":"423","article-title":"Observations on the mechanism of the transmission of plague by fleas","volume":"13","author":"Bacot AW","year":"1914","unstructured":"Bacot AW, Martin CJ. 1914. Observations on the mechanism of the transmission of plague by fleas. J Hyg (Plague Suppl 3) 13:423\u2013439.","journal-title":"J Hyg (Plague Suppl 3)"},{"key":"e_1_3_5_39_2","volume-title":"Public Health Bulletin","author":"Eskey CR","year":"1940","unstructured":"Eskey CR, Haas VH. 1940. Plague in the western part of the United States. In Public Health Bulletin. Vol. 254. U.S. Public Health Service, Washington, D.C."},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/72.1.18"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/77.1.1"},{"key":"e_1_3_5_42_2","volume-title":"Plague","author":"Pollitzer R","year":"1954","unstructured":"Pollitzer R. 1954. Plague. World Health Organization, Geneva."},{"key":"e_1_3_5_43_2","first-page":"425","article-title":"Experiments upon the transmission of plague by fleas","volume":"6","author":"Plague Research Commission","year":"1906","unstructured":"Plague Research Commission. 1906. Experiments upon the transmission of plague by fleas. J Hyg 6:425\u2013482.","journal-title":"J Hyg"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1017\/s0022172400003260"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606831103"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/jme\/tjv128"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/jme\/tjw004"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01162-08"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509544103"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(75)90039-5"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01963151"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00105-08"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00064-11"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408026101"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205750110"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.10.025"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00188-16"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.009"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.04.003"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2116722119"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069972"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04550-9"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.00301-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.00301-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T13:04:10Z","timestamp":1747227850000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.00301-25"}},"subtitle":[],"editor":[{"given":"Alan G.","family":"Barbour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":61,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,14]]}},"alternative-id":["10.1128\/mbio.00301-25"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00301-25","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,14]]},"assertion":[{"value":"2025-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00301-25"}}