{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:47:09Z","timestamp":1791942429948,"version":"4.3.4"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/AuthorWarrantyLicense.v1"},{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | NIH | NIAID | Division of Intramural Research"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,6,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Transmission of\n              <jats:italic>Yersinia pestis<\/jats:italic>\n              by fleas depends on the formation of condensed bacterial aggregates embedded within a gel-like matrix that localizes to the proventricular valve in the flea foregut and interferes with normal blood feeding. This is essentially a bacterial biofilm phenomenon, which at its end stage requires the production of a\n              <jats:italic>Y. pestis<\/jats:italic>\n              exopolysaccharide that bridges the bacteria together in a cohesive, dense biofilm that completely blocks the proventriculus. However, bacterial aggregates are evident within an hour after a flea ingests\n              <jats:italic>Y. pestis<\/jats:italic>\n              , and the bacterial exopolysaccharide is not required for this process. In this study, we characterized the biochemical composition of the initial aggregates and demonstrated that the yersinia murine toxin (Ymt), a\n              <jats:italic>Y. pestis<\/jats:italic>\n              phospholipase D, greatly enhances rapid aggregation following infected mouse blood meals. The matrix of the bacterial aggregates is complex, containing large amounts of protein and lipid (particularly cholesterol) derived from the flea\u2019s blood meal. A similar incidence of proventricular aggregation occurred after fleas ingested whole blood or serum containing\n              <jats:italic>Y. pestis<\/jats:italic>\n              , and intact, viable bacteria were not required. The initial aggregation of\n              <jats:italic>Y. pestis<\/jats:italic>\n              in the flea gut is likely due to a spontaneous physical process termed depletion aggregation that occurs commonly in environments with high concentrations of polymers or other macromolecules and particles such as bacteria. The initial aggregation sets up subsequent binding aggregation mediated by the bacterially produced exopolysaccharide and mature biofilm that results in proventricular blockage and efficient flea-borne transmission.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Yersinia pestis<\/jats:italic>\n              , the bacterial agent of plague, is maintained in nature in mammal-flea-mammal transmission cycles. After a flea feeds on a mammal with septicemic plague, the bacteria rapidly coalesce in the flea\u2019s digestive tract to form dense aggregates enveloped in a viscous matrix that often localizes to the foregut. This represents the initial stage of biofilm development that potentiates transmission of\n              <jats:italic>Y. pestis<\/jats:italic>\n              when the flea later bites a new host. The rapid aggregation likely occurs via a depletion-aggregation mechanism, a non-canonical first step of bacterial biofilm development. We found that the biofilm matrix is largely composed of host blood proteins and lipids, particularly cholesterol, and that the enzymatic activity of a\n              <jats:italic>Y. pestis<\/jats:italic>\n              phospholipase D (Ymt) enhances the initial aggregation.\n              <jats:italic>Y. pestis<\/jats:italic>\n              transmitted by flea bite is likely associated with this host-derived matrix, which may initially shield the bacteria from recognition by the host's intradermal innate immune response.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00124-24","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T13:01:08Z","timestamp":1715259668000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Role of the\n            <i>Yersinia pestis<\/i>\n            phospholipase D (Ymt) in the initial aggregation step of biofilm formation in the flea"],"prefix":"10.1128","volume":"15","author":[{"given":"Clayton O.","family":"Jarrett","sequence":"first","affiliation":[{"name":"Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Leung","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzuki","family":"Motoshi","sequence":"additional","affiliation":[{"name":"Protein Chemistry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Sturdevant","sequence":"additional","affiliation":[{"name":"Genomics Research Section, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Protein Chemistry Section, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forrest H.","family":"Hoyt","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, 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, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090816-093521"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008440"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006859"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1603\/0022-2585(2007)44[672:tdoeto]2.0.co;2"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009092"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010996"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.037952-0"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5273.367"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/422695"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01181-08"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2007.01554.x"},{"key":"e_1_3_5_13_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. 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