{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:47:19Z","timestamp":1791942439465,"version":"4.3.4"},"reference-count":57,"publisher":"Microbiology Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,1]]},"abstract":"<jats:p>Early-phase transmission (EPT) is a recently described model of plague transmission that explains the rapid spread of disease from flea to mammal host during an epizootic. Unlike the traditional blockage-dependent model of plague transmission, EPT can occur when a flea takes its first blood meal after initially becoming infected by feeding on a bacteraemic host. Blockage of the flea gut results from biofilm formation in the proventriculus, mediated by the gene products found in the haemin storage (<jats:italic>hms<\/jats:italic>) locus of the<jats:italic>Yersinia pestis<\/jats:italic>chromosome. Although biofilms are required for blockage-dependent transmission, the role of biofilms in EPT has yet to be determined. An artificial feeding system was used to feed<jats:italic>Xenopsylla cheopis<\/jats:italic>and<jats:italic>Oropsylla montana<\/jats:italic>rat blood spiked with the parental<jats:italic>Y. pestis<\/jats:italic>strain KIM5(pCD1)+, two different biofilm-deficient mutants (\u0394<jats:italic>hmsT<\/jats:italic>, \u0394<jats:italic>hmsR<\/jats:italic>), or a biofilm-overproducer mutant (\u0394<jats:italic>hmsP<\/jats:italic>). Infected fleas were then allowed to feed on na\u00efve Swiss Webster mice for 1\u20134\u2005days after infection, and the mice were monitored for signs of infection. We also determined the bacterial loads of each flea that fed upon na\u00efve mice. Biofilm-defective mutants transmitted from<jats:italic>X. cheopis<\/jats:italic>and<jats:italic>O. montana<\/jats:italic>as efficiently as the parent strain, whereas the EPT efficiency of fleas fed the biofilm-overproducing strain was significantly less than that of fleas fed either the parent or a biofilm-deficient strain. Fleas infected with a biofilm-deficient strain harboured lower bacterial loads 4\u2005days post-infection than fleas infected with the parent strain. Thus, defects in biofilm formation did not prevent flea-borne transmission of<jats:italic>Y. pestis<\/jats:italic>in our EPT model, although biofilm overproduction inhibited efficient EPT. Our results also indicate, however, that biofilms may play a role in infection persistence in the flea.<\/jats:p>","DOI":"10.1099\/mic.0.037952-0","type":"journal-article","created":{"date-parts":[[2010,4,16]],"date-time":"2010-04-16T00:54:54Z","timestamp":1271379294000},"page":"2216-2225","source":"Crossref","is-referenced-by-count":52,"title":["Biofilm formation is not required for early-phase transmission of Yersinia pestis"],"prefix":"10.1099","volume":"156","author":[{"given":"Sara M.","family":"Vetter","sequence":"first","affiliation":[{"name":"Bacterial Diseases Branch, Division of Vector Borne Diseases, National Center for Enteric and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 3150 Rampart Rd, Fort Collins, CO 80521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Eisen","sequence":"additional","affiliation":[{"name":"Bacterial Diseases Branch, Division of Vector Borne Diseases, National Center for 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\u03b2-1,6- N-acetyl-d-glucosamine disrupts the integrity of diverse bacterial biofilms","volume":"187","author":"Itoh","year":"2005","journal-title":"J Bacteriol"},{"key":"R37","first-page":"570","article-title":"The pigmentation of Pasteurella pestis on a defined medium containing haemin","volume":"37","author":"Jackson","year":"1956","journal-title":"Br J Exp Pathol"},{"key":"R38","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1086\/422695","article-title":"Transmission of Yersinia pestis from an infectious biofilm in the flea vector","volume":"190","author":"Jarrett","year":"2004","journal-title":"J Infect Dis"},{"key":"R39","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1099\/13500872-145-8-2117","article-title":"HmsT, a protein essential for expression of the haemin storage (Hms+) phenotype of Yersinia 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