title: Identification of Ata, a multifunctional trimeric autotransporter of Acinetobacter baumannii.
abstract: Acinetobacter baumannii has recently emerged as a highly troublesome nosocomial pathogen, especially in patients in intensive care units and in those undergoing mechanical ventilation. We have identified a surface protein adhesin of A. baumannii, designated the Acinetobacter trimeric autotransporter (Ata), that contains all of the typical features of trimeric autotransporters (TA), including a long signal peptide followed by an N-terminal, surface-exposed passenger domain and a C-terminal domain encoding 4 β-strands. To demonstrate that Ata encoded a TA, we created a fusion protein in which we replaced the entire passenger domain of Ata with the epitope tag V5, which can be tracked with specific monoclonal antibodies, and demonstrated that the C-terminal 101 amino acids of Ata were capable of exporting the heterologous V5 tag to the surface of A. baumannii in a trimeric form. We found that Ata played a role in biofilm formation and bound to various extracellular matrix/basal membrane (ECM/BM) components, including collagen types I, III, IV, and V and laminin. Moreover, Ata mediated the adhesion of whole A. baumannii cells to immobilized collagen type IV and played a role in the survival of A. baumannii in a lethal model of systemic infection in immunocompetent mice. Taken together, these results reveal that Ata is a TA of A. baumannii involved in virulence, including biofilm formation, binding to ECM/BM proteins, mediating the adhesion of A. baumannii cells to collagen type IV, and contributing to the survival of A. baumannii in a mouse model of lethal infection.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Leticia V
authors.initials: LV
authors.lastname: Bentancor
authors.forename: Ana
authors.initials: A
authors.lastname: Camacho-Peiro
authors.forename: Cagla
authors.initials: C
authors.lastname: Bozkurt-Guzel
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
authors.forename: Tomás
authors.initials: T
authors.lastname: Maira-Litrán
mesh_terms: D000151:Acinetobacter Infections; D040981:Acinetobacter baumannii / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development; D003094:Collagen / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D004269:DNA, Bacterial; D026901:Membrane Transport Proteins; D037521:Virulence Factors; D003094:Collagen