A conserved extended signal peptide region directs posttranslational protein translocation via a novel mechanism

Desvaux, Mickaël; Scott-Tucker, Anthony; Turner, Sue M.; Cooper, Lisa M.; Huber, Damon; Nataro, James P.; Henderson, Ian R.

doi:10.1099/mic.0.29091-0

Cited by 60 publications

(53 citation statements)

References 37 publications

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“…The 1,461-aa protein is a typical TAA, possessing all of the expected features of this family. Analysis of the amino acid sequence revealed a putative signal sequence possessing a conserved N-terminal extended signal peptide region (ESPR), which is common to many autotransporter proteins (4,17,19,49), and is predicted to be cleaved after amino acid 50. The analysis also revealed a 1,333-aa passenger domain and a Cterminal translocation unit indicated by the Pfam:YadA (PF03895) domain.…”

Section: Resultsmentioning

confidence: 99%

SadA, a Trimeric Autotransporter from Salmonella enterica Serovar Typhimurium, Can Promote Biofilm Formation and Provides Limited Protection against Infection

et al. 2011

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Salmonella enterica is a major cause of morbidity worldwide and mortality in children and immunocompromised individuals in sub-Saharan Africa. Outer membrane proteins of Salmonella are of significance because they are at the interface between the pathogen and the host, they can contribute to adherence, colonization, and virulence, and they are frequently targets of antibody-mediated immunity. In this study, the properties of SadA, a purported trimeric autotransporter adhesin of Salmonella enterica serovar Typhimurium, were examined. We demonstrated that SadA is exposed on the Salmonella cell surface in vitro and in vivo during infection of mice. Expression of SadA resulted in cell aggregation, biofilm formation, and increased adhesion to human intestinal Caco-2 epithelial cells. Immunization of mice with folded, full-length, purified SadA elicited an IgG response which provided limited protection against bacterial challenge. When anti-SadA IgG titers were enhanced by administering alum-precipitated protein, a modest additional protection was afforded. Therefore, despite SadA having pleiotropic functions, it is not a dominant, protective antigen for antibody-mediated protection against Salmonella.

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Section: Resultsmentioning

confidence: 99%

SadA, a Trimeric Autotransporter from Salmonella enterica Serovar Typhimurium, Can Promote Biofilm Formation and Provides Limited Protection against Infection

et al. 2011

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“…The N-terminal extension or extended signal peptide region is suggested to be involved in the delay of protein translocation for some proteins containing long peptides (13,37,47). However, in other systems, this sequence has no effect on translocation (21).…”

Section: Discussionmentioning

confidence: 99%

The Extended Signal Peptide of the Trimeric Autotransporter EmaA of Aggregatibacter actinomycetemcomitans Modulates Secretion

2011

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The extracellular matrix protein adhesin A (EmaA) of the Gram-negative bacterium Aggregatibacter actinomycetemcomitans is a fibrillar collagen adhesin belonging to the family of trimeric autotransporters. The protein forms antenna-like structures on the bacterial surface required for collagen adhesion. The 202-kDa protein monomers are proposed to be targeted and translocated across the inner membrane by a long signal peptide composed of 56 amino acids. The predicted signal peptide was functionally active in Escherichia coli and A. actinomycetemcomitans using truncated PhoA and Aae chimeric proteins, respectively. Mutations in the signal peptide were generated and characterized for PhoA activity in E. coli. A. actinomycetemcomitans strains expressing EmaA with the identical mutant signal peptides were assessed for cellular localization, surface expression, and collagen binding activity. All of the mutants impaired some aspect of EmaA structure or function. A signal peptide mutant that promoted alkaline phosphatase secretion did not allow any cell surface presentation of EmaA. A second mutant allowed for cell surface exposure but abolished protein function. A third mutant allowed for the normal localization and function of EmaA at 37°C but impaired localization at elevated temperatures. Likewise, replacement of the long EmaA signal peptide with a typical signal peptide also impaired localization above 37°C. The data suggest that the residues of the EmaA signal peptide are required for protein folding or assembly of this collagen adhesin.

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“…3). ESPRs were initially thought to function in cotranslational targeting of large type V family proteins to the periplasm; however, recent studies suggest that the region serves a more subtle function, by regulating the rate of translocation across the inner membrane to avoid an accumulation of misfolded proteins in the periplasm (41,59,60). Bioinformatic analyses have revealed that ESPRs appear to be restricted to type V proteins of Ͼϳ100 kDa in the Beta-and Gammaproteobacteria and are present in approximately 10% of AT proteins (23,24,41,61).…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of Burkholderia pseudomallei Trimeric Autotransporters

2013

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Burkholderia pseudomallei is a tier 1 select agent and the causative agent of melioidosis, a severe and often fatal disease with symptoms ranging from acute pneumonia and septic shock to a chronic infection characterized by abscess formation in the lungs, liver, and spleen. Autotransporters (ATs) are exoproteins belonging to the type V secretion system family, with many playing roles in pathogenesis. The genome of B. pseudomallei strain 1026b encodes nine putative trimeric AT proteins, of which only four have been described. Using a bioinformatic approach, we annotated putative domains within each trimeric AT protein, excluding the well-studied BimA protein, and found short repeated sequences unique to Burkholderia species, as well as an unexpectedly large proportion of ATs with extended signal peptide regions (ESPRs). To characterize the role of trimeric ATs in pathogenesis, we constructed disruption or deletion mutations in each of eight AT-encoding genes and evaluated the resulting strains for adherence to, invasion of, and plaque formation in A549 cells. The majority of the ATs (and/or the proteins encoded downstream) contributed to adherence to and efficient invasion of A549 cells. Using a BALB/c mouse model of infection, we determined the contributions of each AT to bacterial burdens in the lungs, liver, and spleen. At 48 h postinoculation, only one strain, Bp340::pDbpaC, demonstrated a defect in dissemination and/or survival in the liver, indicating that BpaC is required for wildtype virulence in this model.

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A conserved extended signal peptide region directs posttranslational protein translocation via a novel mechanism

Cited by 60 publications

References 37 publications

SadA, a Trimeric Autotransporter from Salmonella enterica Serovar Typhimurium, Can Promote Biofilm Formation and Provides Limited Protection against Infection

SadA, a Trimeric Autotransporter from Salmonella enterica Serovar Typhimurium, Can Promote Biofilm Formation and Provides Limited Protection against Infection

The Extended Signal Peptide of the Trimeric Autotransporter EmaA of Aggregatibacter actinomycetemcomitans Modulates Secretion

Functional Characterization of Burkholderia pseudomallei Trimeric Autotransporters

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