Trimer Stability of YadA Is Critical for Virulence of
            <i>Yersinia enterocolitica</i>

Schütz, Monika; Weiss, Evelyn; Schindler, Magnus K. H.; Hallström, Teresia; Zipfel, Peter F.; Linke, Dirk; Autenrieth, Ingo B.

doi:10.1128/iai.01350-09

Cited by 39 publications

(42 citation statements)

References 50 publications

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“…Our results are in line with previous studies that detected high CXCL1 levels in the sera of mice systemically infected with Y. enterocolitica WT, which correlated with the bacterial burden (43). The process of neutrophil recruitment within individual organs is dictated by inciting infection and the response of organ-specific tissue-resident cells (44).…”

Section: Discussionsupporting

confidence: 82%

Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain

et al. 2016

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Section: Discussionsupporting

confidence: 82%

Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain

et al. 2016

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“…Assays were performed as described elsewhere (47,55) except that LB broth (at pH 8.5) supplemented with Ca 2ϩ and glycerol was used when the aggregation ability of Ec-TaaP, HI4320, or its taaP mutant was tested under alkaline conditions. Briefly, cultures were incubated to late logarithmic phase (postinduction), harvested, washed, and resuspended in phosphate buffer (at the corresponding pH) with an initial OD 600 of ϳ3.0, which was considered 100% for 0 h after the end of log-phase growth (t 0 ).…”

Section: Methodsmentioning

confidence: 99%

Adhesion, Invasion, and Agglutination Mediated by Two Trimeric Autotransporters in the Human Uropathogen Proteus mirabilis

et al. 2010

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Fimbriae of the human uropathogen Proteus mirabilis are the only characterized surface proteins that contribute to its virulence by mediating adhesion and invasion of the uroepithelia. PMI2122 (AipA) and PMI2575 (TaaP) are annotated in the genome of strain HI4320 as trimeric autotransporters with "adhesinlike" and "agglutinating adhesin-like" properties, respectively. The C-terminal 62 amino acids (aa) in AipA and 76 aa in TaaP are homologous to the translocator domains of YadA from Yersinia enterocolitica and Hia from Haemophilus influenzae. Comparative protein modeling using the Hia three-dimensional structure as a template predicted that each of these domains would contain four antiparallel beta sheets and that they formed homotrimers. Recombinant AipA and TaaP were seen as ϳ28 kDa and ϳ78 kDa, respectively, in Escherichia coli, and each also formed high-molecular-weight homotrimers, thus supporting this model. E. coli synthesizing AipA or TaaP bound to extracellular matrix proteins with a 10-to 60-fold-higher level of affinity than the control strain. Inactivation of aipA in P. mirabilis strains significantly (P < 0.01) reduced the mutants' ability to adhere to or invade HEK293 cell monolayers, and the functions were restored upon complementation. A 51-aa-long invasin region in the AipA passenger domain was required for this function. E. coli expressing TaaP mediated autoagglutination, and a taaP mutant of P. mirabilis showed significantly (P < 0.05) more reduced aggregation than HI4320. Gly-247 in AipA and Gly-708 in TaaP were indispensable for trimerization and activity. AipA and TaaP individually offered advantages to P. mirabilis in a murine model. This is the first report characterizing trimeric autotransporters in P. mirabilis as afimbrial surface adhesins and autoagglutinins.

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“…It has been shown that factor H, which binds directly to YadA, acts as a cofactor for factor I-mediated degradation of C3b. However, these data also revealed that only a very small amount of C3b present in the experiments was degraded into iC3b (5,20,21). The amount of C3b typically used in these experiments was considerably lower than that of C3 in human serum.…”

Section: Discussionmentioning

confidence: 69%

“…The exchange of a highly conserved glycine within the C-terminal b-barrel membrane anchor domain by amino acids with larger side chain size (such as threonine, asparagine, histidine) reduces YadA trimer stability and eventually impaired passenger domain translocation. YadA mutants that carried the small amino acids Alanine or Serine instead of Glycine at position 389 resembled wild type expression levels and phenotype except that they were sensitive to complementdependent killing and displayed reduced trimer stability in Western blot (5,7).…”

mentioning

confidence: 99%

“…YadA mediates adhesion to host cells, promotes autoaggregation, and protects from complement-mediated killing (4). Y. enterocolitica virulence in vivo is associated with the presence of YadA, and it is known that the trimeric stability of YadA correlates with pathogenicity in a mouse model of infection (5). Being the prototype of trimeric autotransporter adhesins, YadA consists of three 50-kDa monomers that trimerize upon insertion into the bacterial outer membrane (6).…”

mentioning

confidence: 99%

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Yersinia enterocolitica YadA Mediates Complement Evasion by Recruitment and Inactivation of C3 Products

Schindler

Schütz

Mühlenkamp

et al. 2012

The Journal of Immunology

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Yersinia adhesin A (YadA) is a major virulence factor of Yersinia enterocolitica. YadA mediates host cell binding and autoaggregation and protects the pathogen from killing by the complement system. Previous studies demonstrated that YadA is the most important single factor mediating serum resistance of Y. enterocolitica, presumably by binding C4b binding protein (C4BP) and factor H, which are both complement inhibitors. Factor H acts as a cofactor for factor I-mediated cleavage of C3b into the inactive form iC3b and thus prevents formation of inflammatory effector compounds and the terminal complement complex. In this study, we challenged the current direct binding model of factor H to YadA and show that Y. enterocolitica YadA recruits C3b and iC3b directly, without the need of an active complement cascade or additional serum factors. Enhanced binding of C3b does not decrease survival of YadA-expressing Yersiniae because C3b becomes readily inactivated by factor H and factor I. Binding of factor H to YadA is greatly reduced in the absence of C3. Experiments using Yersinia lacking YadA or expressing YadA with reduced trimeric stability clearly demonstrate that both the presence and full trimeric stability of YadA are essential for complement resistance. A novel mechanism of factor H binding is presented in which YadA exploits recruitment of C3b or iC3b to attract large amounts of factor H. As a consequence, formation of the terminal complement complex is limited and bacterial survival is enhanced. These findings add a new aspect of how Y. enterocolitica effectively evades the host complement system.

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Trimer Stability of YadA Is Critical for Virulence of Yersinia enterocolitica

Cited by 39 publications

References 50 publications

Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain

Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain

Adhesion, Invasion, and Agglutination Mediated by Two Trimeric Autotransporters in the Human Uropathogen Proteus mirabilis

Yersinia enterocolitica YadA Mediates Complement Evasion by Recruitment and Inactivation of C3 Products

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