Host Langerin (CD207) is a receptor for Yersinia pestis phagocytosis and promotes dissemination

Yersinia pestis is a Gram-negative bacterium that causes plague. After Y. pestis overcomes the skin barrier, it encounters antigen-presenting cells (APCs), such as Langerhans and dendritic cells. They transport the bacteria from the skin to the lymph nodes. However, the molecular mechanisms involved in bacterial transmission are unclear. Langerhans cells (LCs) express Langerin (CD207), a calcium-dependent (C-type) lectin. Furthermore, Y. pestis possesses exposed core oligosaccharides. In this study, we show that Y. pestis invades LCs and Langerin-expressing transfectants. However, when the bacterial core oligosaccharides are shielded or truncated, Y. pestis propensity to invade Langerhans and Langerin-expressing cells decreases. Moreover, the interaction of Y. pestis with Langerin-expressing transfectants is inhibited by purified Langerin, a DC-SIGN (DC-specific intercellular adhesion molecule 3 grabbing nonintegrin)-like molecule, an anti-CD207 antibody, purified core oligosaccharides and several oligosaccharides. Furthermore, covering core oligosaccharides reduces the mortality associated with murine infection by adversely affecting the transmission of Y. pestis to lymph nodes. These results demonstrate that direct interaction of core oligosaccharides with Langerin facilitates the invasion of LCs by Y. pestis. Therefore, Langerin-mediated binding of Y. pestis to APCs may promote its dissemination and infection.Peer reviewe

Yersinia pestis Interacts With SIGNR1 (CD209b) for Promoting Host Dissemination and Infection

Yersinia pestis, a Gram-negative bacterium and the etiologic agent of plague, has evolved from Yersinia pseudotuberculosis, a cause of a mild enteric disease. However, the molecular and biological mechanisms of how Y pseudotuberculosis evolved to such a remarkably virulent pathogen, Y pestis, are not clear. The ability to initiate a rapid bacterial dissemination is a characteristic hallmark of Y pestis infection. A distinguishing characteristic between the two Yersinia species is that Y pseudotuberculosis strains possess an O-antigen of lipopolysaccharide (LPS) while Y pestis has lost the O-antigen during evolution and therefore exposes its core LPS. In this study, we showed that Y pestis utilizes its core LPS to interact with SIGNR1 (CD209b), a C-type lectin receptor on antigen presenting cells (APCs), leading to bacterial dissemination to lymph nodes, spleen and liver, and the initiation of a systemic infection. We therefore propose that the loss of O-antigen represents a critical step in the evolution of Y pseudotuberculosis into Y pestis in terms of hijacking APCs, promoting bacterial dissemination and causing the plague.Peer reviewe

Diversity of Francisella tularensis Subsp. holarctica Lineages, China

We analyzed 10 isolates of Francisella tularensis subspecies holarctica from China and assigned them to known clades by using canonical single-nucleotide polymorphisms. We found 4 diverse subtypes, including 3 from the most basal lineage, biovar japonica. This result indicates unprecedented levels of diversity from a single region and suggests new models for emergence

Complete Genome Sequences of Yersinia pestis from Natural Foci in China▿

Yersinia pestis, the causative agent of plague, is a deadly bacterium that affects humans. Strain D106004 was isolated from a new plague focus in Yulong County, China, in 2006. To gain insights into the epidemic origin, we have sequenced the genomes of D106004 and strains Z176003 and D182038, isolated from neighboring regions

Reemergence of human plague in Yunnan, China in 2016

<div><p>The third plague pandemic originated from Yunnan Province, China in the middle of the 19^th century. The last human plague epidemic in Yunnan occurred from 1986–2005. On June 6, 2016, a case of human plague was reported in the Xishuangbanna Prefecture, Yunnan. The patient suffered from primary septicemic plague after exposure to a dead house rat (<i>Rattus flavipectus</i>), which has been identified as the main plague reservoir in the local epizootic area. Moreover, a retrospective investigation identified another bubonic plague case in this area. Based on these data, human plague reemerged after a silent period of ten years. In this study, three molecular typing methods, including a clustered regularly interspaced short palindromic repeats (CRISPR) analysis, different region analysis (DFR), and multiple-locus variable number of tandem repeats analysis (MLVA), were used to illustrate the molecular characteristics of <i>Yersinia pestis</i> (<i>Y</i>. <i>pestis</i>) strains isolated in Yunnan. The DFR profiles of the strains isolated in Yunnan in 2016 were the same as the strains that had previously been isolated in this <i>Rattus flavipectus</i> plague focus. The c3 spacer present in the previously isolated strains was absent in the spacer arrays of the Ypc CRISPR loci of the strains isolated in 2016. The MLVA analysis using MLVA (14+12) showed that the strains isolated from the human plague case and host animal plague infection in 2016 in Yunnan displayed different molecular patterns than the strains that had previously been isolated from Yunnan and adjacent provinces.</p></div

Dendrogram of the <i>Y</i>. <i>pestis</i> strains isolated in Yunnan obtained using the MLVA14 scheme.

<p>The number on the dendrogram line indicates the MLVA14 scheme subclade.</p

Minimum spanning tree (MST) of the isolates in the MLVA14-06 subclade obtained using the MLVA(14+12) scheme.

<p>Thick solid lines connect types that differed in a single VNTR locus, thin solid lines connect types that differed in 2 VNTR loci, and other lines connect types that differed in more than 2 VNTR loci. Circles with different colors indicate prefectures in Yunnan or other provinces or strains isolated in Burma. The year in which the isolate was obtained is indicated by the lineages. The numbers on the branches indicate the different numbers of VNTR loci. If two neighboring types did not differ in more than 2 VNTR loci, they would be surrounded by a halo of the same color.</p

Genome Rearrangements of Completely Sequenced Strains of Yersinia pestis▿ ‡

Yersinia pestis has caused three worldwide plagues in human history that have led to innumerable deaths. We have completely sequenced the genomes of two strains (D106004 and D182038) of Y. pestis isolated from Yunnan Province of China. The most striking finding of our study is that large amounts of genome rearrangement events exist between the genomes of two Yunnan strains despite being isolated from two foci only 50 kilometers apart. When we compared the genome sequences of the Yunnan strains with six strains (CO92, KIM, 91001, Antiqua, Nepal516, and Pestoides F) of Y. pestis sequenced previously, we found that the genomes of Y. pestis were divided into 61 relatively independent segments. Pairwise comparisons of all 61 segments among eight strains showed that the Yunnan strains were most closely related to strain CO92. We concluded that Y. pestis genomes consist of segments that can change their positions and directions within the genomes caused by genome rearrangements, and our study confirmed the inference that the third plague pandemic originated in Yunnan since the genome sequences of Yunnan strains were closest to the strain CO92 isolated from the United States