In silico comparison of Yersinia pestis and Yersinia pseudotuberculosis transcriptomes reveals a higher expression level of crucial virulence determinants in the plague bacillus

Chauvaux, Sylvie; Dillies, Marie‐Agnès; Marceau, Michaël; Rosso, Marie-Laure; Rousseau, Sandrine; Moszer, Ivan; Simonet, Michel; Carniel, Élisabeth

doi:10.1016/j.ijmm.2010.08.013

Cited by 24 publications

(19 citation statements)

References 53 publications

(61 reference statements)

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“…The reason for this difference is unclear but is likely due to differences between regulation of the calcium response between Y. pestis and the enteric Yersinia spp. (45,46). Evaluation of the tip complex using chemical cross-linking demonstrated that YscFD28AD46A polymers were unable to generate the same HMW LcrV complexes observed in the WT, despite detection of LcrV on the bacterial surface by immunofluorescence.…”

Section: Discussionmentioning

confidence: 98%

A Mutant with Aberrant Extracellular LcrV-YscF Interactions Fails To Form Pores and Translocate Yop Effector Proteins but Retains the Ability To Trigger Yop Secretion in Response to Host Cell Contact

et al. 2013

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The plasmid-encoded type three secretion system (TTSS) of Yersinia spp. is responsible for the delivery of effector proteins into cells of the innate immune system, where these effectors disrupt the target cells' activity. Successful translocation of effectors into mammalian cells requires Yersinia to both insert a translocon into the host cell membrane and sense contact with host cells. To probe the events necessary for translocation, we investigated protein-protein interactions among TTSS components of the needle-translocon complex using a chemical cross-linking-based approach. We detected extracellular protein complexes containing YscF, LcrV, and YopD that were dependent upon needle formation. The formation of these complexes was evaluated in a secretion-competent but translocation-defective mutant, the YscFD28AD46A strain (expressing YscF with the mutations D28A and D46A). We found that one of the YscF and most of the LcrV and YopD cross-linked complexes were nearly absent in this mutant. Furthermore, the YscFD28AD46A strain did not support YopB insertion into mammalian membranes, supporting the idea that the LcrV tip complex is required for YopB insertion and translocon formation. However, the YscFD28AD46A strain did secrete Yops in the presence of host cells, indicating that a translocation-competent tip complex is not required to sense contact with host cells to trigger Yop secretion. In conclusion, in the absence of cross-linkable LcrV-YscF interactions, translocon insertion is abolished, but Yersinia still retains the ability to sense cell contact.

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Section: Discussionmentioning

confidence: 98%

A Mutant with Aberrant Extracellular LcrV-YscF Interactions Fails To Form Pores and Translocate Yop Effector Proteins but Retains the Ability To Trigger Yop Secretion in Response to Host Cell Contact

et al. 2013

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“…While outside the scope of this work, evidence is accumulating that regulatory differences exist between Y. pestis and Y. pseudotuberculosis, resulting in the altered expression of virulence factors (15); some of these differences may be related to the small RNA-stabilizing regulator Hfq and alterations in the compositions of sRNAs in Y. pestis versus Y. pseudotuberculosis (9,32). Just as the coding sequences of yapK in Y. pestis and Y. pseudotuberculosis share a high level of sequence identity, the promoter regions of these genes are also nearly identical.…”

Section: Figmentioning

confidence: 99%

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

2012

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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.

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“…The regions of greatest similarity are the transmembrane domains, while the greatest sequence diversity is found in the surface exposed loops, which likely mediate host interactions. In Y. pestis , Ail is one of the most highly transcribed genes and comprises approximately 20–30% of the outer membrane proteome when grown at 37°C . Ail plays multiple roles in virulence, including facilitation of Yop delivery into host cells, adhesion/invasion, and serum resistance .…”

Section: Introductionmentioning

confidence: 99%

Yersinia pestisAil recruitment of C4b‐binding protein leads to factor I‐mediated inactivation of covalently and noncovalently bound C4b

Skurnik

Blom

et al. 2014

Eur J Immunol

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The outer membrane protein Ail of Yersinia pestis mediates several virulence functions, including serum resistance. Here, we demonstrate that Ail binds C4b-binding protein (C4BP), the primary fluid-phase regulator of the classical and lectin pathways. Noncovalent binding of C4 and C4b to Ail was also observed. C4BP bound to Ail can act as a cofactor to the serine protease factor I (fI) in the cleavage of fluid-phase C4b. Employing a panel of C4BP alpha-chain mutants, we observed that the absence of complement control protein domain 6 and 8 reduced binding to Ail. Immunoblot analysis of normal human serum (NHS)-treated bacteria revealed minimal C4b alpha'-chain complexes with bacterial outer membrane targets. Addition of the anti-C4BP monoclonal antibody MK104 to NHS restored C4b-alpha' chain target complexes, suggesting that C4b binds covalently to targets on the Y. pestis surface. C4b bound to Ail noncovalently was also cleaved in a C4BP and fI-dependent manner, leaving the C4c fragment bound to Ail. MK104 also prevented the cleavage of noncovalently bound C4b. Collectively, these data suggest that when C4BP is bound to Ail, fI can cleave and inactivate C4b that has bound covalently to bacterial surface structures as well as C4b bound noncovalently to Ail. Keywords: Ail r C4b-binding protein r Complement r YersiniaAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionYersinia pestis is a rod-shaped, Gram negative, nonmotile, facultative anaerobic bacterium, and one of the most virulent pathogens known to man. Over the course of three pandemics, this pathogen has claimed millions of human lives throughout history. Y. pestis can be transferred from a rodent carrier to a human host via Correspondence: Dr. Derek K. Ho e-mail: derek.ho@helsink.fi the bite of an infected flea, or by direct human-to-human transmission in the case of pneumonic plague. Y. pestis remains endemic in certain parts of the world and is a reemerging disease in Africa [1]. The high mortality if left untreated, the absence of an effective vaccine, the emergence of antibiotic resistant strains [2], and the possibility of bioterrorism justify continued research into this pathogen [3].Y. pestis possesses a battery of mechanisms that disarm the host immune response. For example, Y. pestis produces a tetra-acylated LPS that is a poor inducer of TLR 4 [4]. The pYV (pCD1) virulence plasmid encodes a type III secretion system and associated C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 742-751 Immunity to infection 743 effector proteins (Yops), which confer the ability to disrupt host cell signaling and the actin cytoskeleton [5]. Plasmid pPCP1 encodes the plasminogen activator Pla, which degrades fibrin clots and extracellular matrix components, facilitating bacterial dissemination. Plasmid pMT1 encodes the antiphagocytic capsular antigen, F1 [6]. Y. pestis is highly resistant to the bactericidal action of serum due to the presen...

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In silico comparison of Yersinia pestis and Yersinia pseudotuberculosis transcriptomes reveals a higher expression level of crucial virulence determinants in the plague bacillus

Cited by 24 publications

References 53 publications

A Mutant with Aberrant Extracellular LcrV-YscF Interactions Fails To Form Pores and Translocate Yop Effector Proteins but Retains the Ability To Trigger Yop Secretion in Response to Host Cell Contact

A Mutant with Aberrant Extracellular LcrV-YscF Interactions Fails To Form Pores and Translocate Yop Effector Proteins but Retains the Ability To Trigger Yop Secretion in Response to Host Cell Contact

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

Yersinia pestisAil recruitment of C4b‐binding protein leads to factor I‐mediated inactivation of covalently and noncovalently bound C4b

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