HadA is an atypical new multifunctional trimeric coiled-coil adhesin ofHaemophilus influenzaebiogroupaegyptius, which promotes entry into host cells
| Autor: | Anna Rita Taddei, Davide Serruto, Mariagrazia Pizza, Beatrice Aricò, Rino Rappuoli, Marco R. Oggioni, Sonja Höhle, Stefania Bambini, Esteban Veiga, Maria Scarselli, Tiziana Spadafina, Ilaria Ferlenghi, Vega Masignani, Pascale Cossart, Mogens Kilian, Silvana Savino, Maurizio Comanducci |
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| Přispěvatelé: | Serruto D, Spadafina T, Scarselli M, Bambini S, Comanducci M, Höhle S, Kilian M, Veiga E, Cossart P, Oggioni MR, Savino S, Ferlenghi I, Taddei AR, Rappuoli R, Pizza M, Masignani V, Aricò B |
| Rok vydání: | 2009 |
| Předmět: |
DNA
Bacterial Models Molecular Haemophilus influenzae biogroup aegyptius Sequence analysis Molecular Sequence Data Immunology Protein function Sequence Homology Bacterial genome size medicine.disease_cause Microbiology Bacterial Adhesion Cell Line Bacterial Proteins Virology medicine Humans Brazilian purpuric fever Adhesins Bacterial Protein Structure Quaternary Escherichia coli Phylogeny Binding Sites biology Neisseria meningitidis Computational Biology Genomics Sequence Analysis DNA medicine.disease biology.organism_classification Entry into host Haemophilus influenzae Bacterial adhesin Protein structure |
| Zdroj: | Serruto, D, Spadafina, T, Scarselli, M, Bambini, S, Comanducci, M, Höhle, S, Kilian, M, Veiga, E, Cossart, P, Oggioni, M R, Savino, S, Ferlenghi, I, Taddei, A R, Rappuoli, R, Pizza, M, Masignani, V & Aricò, B 2009, ' HadA is an atypical new multifunctional trimeric coiled-coil adhesin of Haemophilus influenzae biogroup aegyptius, which promotes entry into host cells ', Cellular Microbiology, vol. 11, pp. 1044-1063 . https://doi.org/10.1111/j.1462-5822.2009.01306.x |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/j.1462-5822.2009.01306.x |
| Popis: | Summary The Oca (Oligomeric coiled-coil adhesin) family is a subgroup of the bacterial trimeric autotrans- porter adhesins, which includes structurally related proteins, such as YadA of Yersinia entero- colitica and NadA of Neisseria meningitidis. In this study, we searched in silico for novel members of this family in bacterial genomes and identified HadA (Haemophilus adhesin A), a trimeric autotransporter expressed only by Haemophilus influenzae biogroup aegyptius causing Brazilian purpuric fever (BPF), a fulminant septicemic disease of children. By comparative genomics and sequence analysis we predicted that the hadA gene is harboured on a mobile genetic element unique to BPF isolates. Biological analysis of HadA in the native background was limited because this organism is not amenable to genetic manipulation. Alternatively, we demonstrated that expression of HadA confers to a non-invasive Escherichia coli strain the ability to adhere to human cells and to extracellular matrix proteins and to induce in vitro bacterial aggregation and microcolony formation. Intriguingly, HadA is pre- dicted to lack the typical N-terminal head domain of Oca proteins generally associated with cellular receptor binding. We propose here a structural model of the HadA coiled-coil stalk and show that the N-terminal region is still responsible of the binding activity and a KGD motif plays a role. Interestingly, HadA promotes bacterial entry into mammalian cells. Our results show a cytoskeleton re-arrangement and an involvement of clathrin in the HadA-mediated internalization. These data give new insights on the structure-function relationship of oligomeric coiled-coil adhesins and suggest a potential role of this protein in the pathogenesis of BPF. |
| Databáze: | OpenAIRE |
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