scholarly journals Adhesive Properties of YapV and Paralogous Autotransporter Proteins of Yersinia pestis

2015 ◽  
Vol 83 (5) ◽  
pp. 1809-1819 ◽  
Author(s):  
Manoj K. M. Nair ◽  
Leon De Masi ◽  
Min Yue ◽  
Estela M. Galván ◽  
Huaiqing Chen ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Yersinia Pseudotuberculosis ◽  
Alveolar Epithelial Cells ◽  
Adhesive Properties ◽  
Content Type ◽  
Amino Terminal ◽  
New Genes ◽  
Ecm Proteins ◽  
Typical Sequence ◽  
Paralogous Proteins

Yersinia pestisis the causative agent of plague. This bacterium evolved from an ancestral enteroinvasiveYersinia pseudotuberculosisstrain by gene loss and acquisition of new genes, allowing it to use fleas as transmission vectors. Infection frequently leads to a rapidly lethal outcome in humans, a variety of rodents, and cats. This study focuses on theY. pestisKIMyapVgene and its product, recognized as an autotransporter protein by its typical sequence, outer membrane localization, and amino-terminal surface exposure. Comparison ofYersiniagenomes revealed that DNA encoding YapV or each of three individual paralogous proteins (YapK, YapJ, and YapX) was present as a gene or pseudogene in a strain-specific manner and only inY. pestisandY. pseudotuberculosis. YapV acted as an adhesin for alveolar epithelial cells and specific extracellular matrix (ECM) proteins, as shown with recombinantEscherichia coli,Y. pestis, or purified passenger domains. Like YapV, YapK and YapJ demonstrated adhesive properties, suggesting that their previously relatedin vivoactivity is due to their capacity to modulate binding properties ofY. pestisin its hosts, in conjunction with other adhesins. A differential host-specific type of binding to ECM proteins by YapV, YapK, and YapJ suggested that these proteins participate in broadening the host range ofY. pestis. A phylogenic tree including 36Y. pestisstrains highlighted an association between the gene profile for the four paralogous proteins and the geographic location of the corresponding isolated strains, suggesting an evolutionary adaption ofY. pestisto specific local animal hosts or reservoirs.

scholarly journals Complete Genome Assembly of Yersinia pseudotuberculosis IP2666pIB1

2019 ◽  
Vol 8 (7) ◽  
Author(s):  
Adam Zoubeidi ◽  
Leah Schwiesow ◽  
Victoria Auerbuch ◽  
Hanh N. Lam
Keyword(s):  
Yersinia Pestis ◽  
Genome Assembly ◽  
Complete Genome ◽  
Yersinia Pseudotuberculosis ◽  
Model Organism ◽  
Genomic Analysis ◽  
Bacterial Pathogenesis ◽  
Bacterial Virulence ◽  
Human Pathogen ◽  
Content Type

Yersinia pseudotuberculosis, closely related to Yersinia pestis, is a human pathogen and model organism for studying bacterial pathogenesis. To aid in genomic analysis and understanding bacterial virulence, we sequenced and assembled the complete genome of the human pathogen Yersinia pseudotuberculosis IP2666pIB1.

scholarly journals A Type III Secretion System Inhibitor Targets YopD while Revealing Differential Regulation of Secretion in Calcium-Blind Mutants of Yersinia pestis

2013 ◽  
Vol 58 (2) ◽  
pp. 839-850 ◽  
Author(s):  
Danielle L. Jessen ◽  
David S. Bradley ◽  
Matthew L. Nilles
Keyword(s):  
Yersinia Pestis ◽  
Type Iii Secretion ◽  
Yersinia Pseudotuberculosis ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Secretion Systems ◽  
Content Type ◽  
Type Iii ◽  
Regulatory Processes ◽  
Secretion Inhibition

ABSTRACTNumerous Gram-negative pathogens rely upon type III secretion (T3S) systems to cause disease. Several small-molecule inhibitors of the type III secretion systems have been identified; however, few targets of these inhibitors have been elucidated. Here we report that 2,2′-thiobis-(4-methylphenol) (compound D), inhibits type III secretion inYersinia pestis,Yersinia pseudotuberculosis, andPseudomonas aeruginosa. YopD, a protein involved in the formation of the translocon and regulatory processes of the type III secretion system, appears to play a role in the inhibition of secretion by compound D. The use of compound D in T3S regulatory mutants demonstrated a difference in secretion inhibition in the presence and absence of calcium. Interestingly, compound D was effective only under conditions without calcium, indicating that a secretion-active needle structure may be necessary for compound D to inhibit secretion.

scholarly journals Combinational Deletion of Three Membrane Protein-Encoding Genes Highly Attenuates Yersinia pestis while Retaining Immunogenicity in a Mouse Model of Pneumonic Plague

2015 ◽  
Vol 83 (4) ◽  
pp. 1318-1338 ◽  
Author(s):  
Bethany L. Tiner ◽  
Jian Sha ◽  
Michelle L. Kirtley ◽  
Tatiana E. Erova ◽  
Vsevolod L. Popov ◽  
...  
Keyword(s):  
Mouse Model ◽  
Yersinia Pestis ◽  
Double Mutant ◽  
Lethal Dose ◽  
Bactericidal Effect ◽  
Alveolar Epithelial Cells ◽  
Triple Mutant ◽  
Pneumonic Plague ◽  
Content Type

Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuatedYersinia pestisCO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted theailgene (encoding theattachment-invasionlocus) from wild-type (WT) strain CO92 or itslppsingle and ΔlppΔmsbBdouble mutants. While the Δailsingle mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the ΔlppΔaildouble mutant and the ΔlppΔmsbBΔailtriple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time byin vivoimaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of theailgene from the ΔlppΔmsbBdouble mutant severely attenuatedY. pestisCO92 to evoke pneumonic plague in a mouse model while retaining the required immunogenicity needed for subsequent protection against infection.

scholarly journals A Trimeric Autotransporter Enhances Biofilm Cohesiveness in Yersinia pseudotuberculosis but Not in Yersinia pestis

2020 ◽  
Vol 202 (20) ◽  
Author(s):  
Joshua T. Calder ◽  
Nicholas D. Christman ◽  
Jessica M. Hawkins ◽  
David L. Erickson
Keyword(s):  
Extracellular Matrix ◽  
Yersinia Pestis ◽  
Yersinia Pseudotuberculosis ◽  
Extracellular Polysaccharide ◽  
Proteinase K ◽  
Signaling Cascade ◽  
Content Type ◽  
Regulatory Cascade ◽  
Biofilm Production ◽  
Cell Cell

ABSTRACT Cohesion of biofilms made by Yersinia pestis and Yersinia pseudotuberculosis has been attributed solely to an extracellular polysaccharide matrix encoded by the hms genes (Hms-dependent extracellular matrix [Hms-ECM]). However, mutations in the Y. pseudotuberculosis BarA/UvrY/CsrB regulatory cascade enhance biofilm stability without dramatically increasing Hms-ECM production. We found that treatment with proteinase K enzyme effectively destabilized Y. pseudotuberculosis csrB mutant biofilms, suggesting that cell-cell interactions might be mediated by protein adhesins or extracellular matrix proteins. We identified an uncharacterized trimeric autotransporter lipoprotein (YPTB2394), repressed by csrB, which has been referred to as YadE. Biofilms made by a ΔyadE mutant strain were extremely sensitive to mechanical disruption. Overexpression of yadE in wild-type Y. pseudotuberculosis increased biofilm cohesion, similar to biofilms made by csrB or uvrY mutants. We found that the Rcs signaling cascade, which represses Hms-ECM production, activated expression of yadE. The yadE gene appears to be functional in Y. pseudotuberculosis but is a pseudogene in modern Y. pestis strains. Expression of functional yadE in Y. pestis KIM6+ weakened biofilms made by these bacteria. This suggests that although the YadE autotransporter protein increases Y. pseudotuberculosis biofilm stability, it may be incompatible with the Hms-ECM production that is essential for Y. pestis biofilm production in fleas. Inactivation of yadE in Y. pestis may be another instance of selective gene loss in the evolution of flea-borne transmission by this species. IMPORTANCE The evolution of Yersinia pestis from its Y. pseudotuberculosis ancestor involved gene acquisition and gene losses, leading to differences in biofilm production. Characterizing the unique biofilm features of both species may provide better understanding of how each adapts to its specific niches. This study identifies a trimeric autotransporter, YadE, that promotes biofilm stability of Y. pseudotuberculosis but which has been inactivated in Y. pestis, perhaps because it is not compatible with the Hms polysaccharide that is crucial for biofilms inside fleas. We also reveal that the Rcs signaling cascade, which represses Hms expression, activates YadE in Y. pseudotuberculosis. The ability of Y. pseudotuberculosis to use polysaccharide or YadE protein for cell-cell adhesion may help it produce biofilms in different environments.

scholarly journals Evaluation of the Role of theopgGHOperon in Yersinia pseudotuberculosis and Its Deletion during the Emergence of Yersinia pestis

2015 ◽  
Vol 83 (9) ◽  
pp. 3638-3647 ◽  
Author(s):  
Kévin Quintard ◽  
Amélie Dewitte ◽  
Angéline Reboul ◽  
Edwige Madec ◽  
Sébastien Bontemps-Gallo ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Cell Size ◽  
Biofilm Formation ◽  
Yersinia Pseudotuberculosis ◽  
Acyl Carrier Protein ◽  
Size Control ◽  
Growth Conditions ◽  
Mammalian Host ◽  
Dickeya Dadantii ◽  
Content Type

TheopgGHoperon encodes glucosyltransferases that synthesize osmoregulated periplasmic glucans (OPGs) from UDP-glucose, using acyl carrier protein (ACP) as a cofactor. OPGs are required for motility, biofilm formation, and virulence in various bacteria. OpgH also sequesters FtsZ in order to regulate cell size according to nutrient availability.Yersinia pestis(the agent of flea-borne plague) lost theopgGHoperon during its emergence from the enteropathogenYersinia pseudotuberculosis. When expressed in OPG-negative strains ofEscherichia coliandDickeya dadantii,opgGHfromY. pseudotuberculosisrestored OPGs synthesis, motility, and virulence. However,Y. pseudotuberculosisdid not produce OPGs (i) under various growth conditions or (ii) when overexpressing itsopgGHoperon, itsgalUFoperon (governing UDP-glucose), or theopgGHoperon or Acp fromE. coli. A ΔopgGHY. pseudotuberculosisstrain showed normal motility, biofilm formation, resistance to polymyxin and macrophages, and virulence but was smaller. Consistently,Y. pestiswas smaller thanY. pseudotuberculosiswhen cultured at ≥37°C, except when the plague bacillus expressedopgGH.Y. pestisexpressingopgGHgrew normally in serum and within macrophages and was fully virulent in mice, suggesting that small cell size was not advantageous in the mammalian host. Lastly,Y. pestisexpressingopgGHwas able to infectXenopsylla cheopisfleas normally. Our results suggest an evolutionary scenario whereby an ancestralYersiniastrain lost a factor required for OPG biosynthesis but keptopgGH(to regulate cell size). TheopgGHoperon was presumably then lost because OpgH-dependent cell size control became unnecessary.

scholarly journals Yersinia pestis: the Natural History of Plague

2020 ◽  
Vol 34 (1) ◽  
Author(s):  
R. Barbieri ◽  
M. Signoli ◽  
D. Chevé ◽  
C. Costedoat ◽  
S. Tzortzis ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Bronze Age ◽  
Contaminated Soils ◽  
Yersinia Pseudotuberculosis ◽  
Close Contact ◽  
Point Of Care ◽  
Clonal Evolution ◽  
Human Populations ◽  
African Countries ◽  
Content Type

SUMMARY The Gram-negative bacterium Yersinia pestis is responsible for deadly plague, a zoonotic disease established in stable foci in the Americas, Africa, and Eurasia. Its persistence in the environment relies on the subtle balance between Y. pestis-contaminated soils, burrowing and nonburrowing mammals exhibiting variable degrees of plague susceptibility, and their associated fleas. Transmission from one host to another relies mainly on infected flea bites, inducing typical painful, enlarged lymph nodes referred to as buboes, followed by septicemic dissemination of the pathogen. In contrast, droplet inhalation after close contact with infected mammals induces primary pneumonic plague. Finally, the rarely reported consumption of contaminated raw meat causes pharyngeal and gastrointestinal plague. Point-of-care diagnosis, early antibiotic treatment, and confinement measures contribute to outbreak control despite residual mortality. Mandatory primary prevention relies on the active surveillance of established plague foci and ectoparasite control. Plague is acknowledged to have infected human populations for at least 5,000 years in Eurasia. Y. pestis genomes recovered from affected archaeological sites have suggested clonal evolution from a common ancestor shared with the closely related enteric pathogen Yersinia pseudotuberculosis and have indicated that ymt gene acquisition during the Bronze Age conferred Y. pestis with ectoparasite transmissibility while maintaining its enteric transmissibility. Three historic pandemics, starting in 541 AD and continuing until today, have been described. At present, the third pandemic has become largely quiescent, with hundreds of human cases being reported mainly in a few impoverished African countries, where zoonotic plague is mostly transmitted to people by rodent-associated flea bites.

scholarly journals Evolution and Virulence Contributions of the Autotransporter Proteins YapJ and YapK of Yersinia pestis CO92 and Their Homologs in Y. pseudotuberculosis IP32953

2012 ◽  
Vol 80 (10) ◽  
pp. 3693-3705 ◽  
Author(s):  
Jonathan D. Lenz ◽  
Brenda R. S. Temple ◽  
Virginia L. Miller
Keyword(s):  
Yersinia Pestis ◽  
Yersinia Pseudotuberculosis ◽  
Systemic Infection ◽  
Content Type ◽  
Sequence Identity ◽  
Homologous Genes ◽  
C Terminus ◽  
Gastrointestinal Pathogen ◽  
Numerous Type ◽  
High Level

ABSTRACTYersinia pestis, the causative agent of plague, evolved from the gastrointestinal pathogenYersinia pseudotuberculosis. Both species have numerous type Va autotransporters, most of which appear to be highly conserved. InY. pestisCO92, the autotransporter genesyapKandyapJshare a high level of sequence identity. By comparingyapKandyapJto three homologous genes inY. pseudotuberculosisIP32953 (YPTB0365, YPTB3285, and YPTB3286), we show thatyapKis conserved inY. pseudotuberculosis, whileyapJis unique toY. pestis. All of these autotransporters exhibit >96% identity in the C terminus of the protein and identities ranging from 58 to 72% in their N termini. By extending this analysis to include homologous sequences from numerousY. pestisandY. pseudotuberculosisstrains, we determined that these autotransporters cluster into a YapK (YPTB3285) class and a YapJ (YPTB3286) class. The YPTB3286-like gene of mostY. pestisstrains appears to be inactivated, perhaps in favor of maintainingyapJ. Since autotransporters are important for virulence in many bacterial pathogens, includingY. pestis, any change in autotransporter content should be considered for its impact on virulence. Using established mouse models ofY. pestisinfection, we demonstrated that despite the high level of sequence identity,yapKis distinct fromyapJin its contribution to disseminatedY. pestisinfection. In addition, a mutant lacking both of these genes exhibits an additive attenuation, suggesting nonredundant roles foryapJandyapKin systemicY. pestisinfection. However, the deletion of the homologous genes inY. pseudotuberculosisdoes not seem to impact the virulence of this organism in orogastric or systemic infection models.

scholarly journals Homophilic adhesion between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds

1993 ◽  
Vol 122 (4) ◽  
pp. 951-960 ◽  
Author(s):  
H Zhou ◽  
A Fuks ◽  
G Alcaraz ◽  
TJ Bolling ◽  
CP Stanners
Keyword(s):  
Carcinoembryonic Antigen ◽  
Cell Aggregation ◽  
Intercellular Adhesion ◽  
Cell Surface Expression ◽  
Adhesive Properties ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Internal Repeat ◽  
Immunoglobulin Supergene Family ◽  
Supergene Family

Both carcinoembryonic antigen (CEA) and neural cell adhesion molecule (NCAM) belong to the immunoglobulin supergene family and have been demonstrated to function as homotypic Ca(++)-independent intercellular adhesion molecules. CEA and NCAM cannot associate heterotypically indicating that they have different binding specificities. To define the domains of CEA involved in homotypic interaction, hybrid cDNAs consisting of various domains from CEA and NCAM were constructed and were transfected into a CHO-derived cell line; stable transfectant clones showing cell surface expression of CEA/NCAM chimeric-proteins were assessed for their adhesive properties by homotypic and heterotypic aggregation assays. The results indicate that all five of the Ig(C)-like domains of NCAM are required for intercellular adhesion while the COOH-terminal domain containing the fibronectin-like repeats is dispensable. The results also show that adhesion mediated by CEA involves binding between the Ig(V)-like amino-terminal domain and one of the Ig(C)-like internal repeat domains: thus while transfectants expressing constructs containing either the N domain or the internal domains alone were incapable of homotypic adhesion, they formed heterotypic aggregates when mixed. Furthermore, peptides consisting of both the N domain and the third internal repeat domain of CEA blocked CEA-mediated cell aggregation, thus providing direct evidence for the involvement of the two domains in adhesion. We therefore propose a novel model for interactions between immunoglobulin supergene family members in which especially strong binding is effected by double reciprocal interactions between the V-like domains and C-like domains of antiparallel CEA molecules on apposing cell surfaces.

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