Protein Secretion in Gram-Negative Bacteria via the Autotransporter Pathway

Dautin, Nathalie; Bernstein, Harris

doi:10.1146/annurev.micro.61.080706.093233

Cited by 259 publications

(258 citation statements)

References 97 publications

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“…In contrast, we found here by analytical size-exclusion chromatography (SEC) that Sca2 is a monomer (Fig. S5), which is also consistent with the fact that Sca2 has a monomeric type of translocator domain (14). How does a monomeric protein track the two long-pitch helices of the filament?…”

supporting

confidence: 84%

“…The signal peptide targets autotransporter proteins for passage across the inner bacterial membrane. This first step is followed by insertion of the translocator domain into the outer membrane, where it forms a pore through which the passenger domain is translocated and either cleaved or held tethered on the surface of the bacterium (14). By immunofluorescence microscopy, Sca2 has been localized to the actin tail-associated surface of R. parkeri (13), and disruption of the sca2 gene in R. rickettsii inhibits actin-tail formation and motility (12), which also results in reduced virulence.…”

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confidence: 99%

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Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism

Madasu

Suarez

Kast

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Sca2 (surface cell antigen 2) is the only bacterial protein known to promote both actin filament nucleation and profilin-dependent elongation, mimicking eukaryotic formins to assemble actin comet tails for Rickettsia motility. We show that Sca2's functional mimicry of formins is achieved through a unique mechanism. Unlike formins, Sca2 is monomeric, but has N-and C-terminal repeat domains (NRD and CRD) that interact with each other for processive barbed-end elongation. The crystal structure of NRD reveals a previously undescribed fold, consisting of helix-loop-helix repeats arranged into an overall crescent shape. CRD is predicted to share this fold and might form together with NRD, a doughnut-shaped formin-like structure. In between NRD and CRD, proline-rich sequences mediate the incorporation of profilin-actin for elongation, and WASP-homology 2 (WH2) domains recruit actin monomers for nucleation. Sca2's α-helical fold is unusual among Gram-negative autotransporters, which overwhelmingly fold as β-solenoids. Rickettsia has therefore "rediscovered" formin-like actin nucleation and elongation.passenger domain | translocator domain | spotted fever M any bacterial pathogens use the actin cytoskeleton of host eukaryotic cells for invasion and motility (1, 2). In so doing, bacteria often resort to mimicry by expressing proteins that adopt core functions of key actin cytoskeletal components, particularly actin filament nucleation and elongation factors. However, bacterial proteins tend to bypass the elaborate regulatory networks characteristic of their eukaryotic counterparts, offering a rare opportunity to dissect their functions within a simplified system (2, 3), with implications for our understanding of pathogenicity and the eukaryotic actin cytoskeleton alike.Rickettsiae are obligate intracellular Gram-negative pathogens that are transmitted to humans via arthropod vectors, such as ticks, fleas, and lice (4). Rickettsia species are responsible for a number of severe human diseases, including typhus and spotted fever (5). The spotted fever group, including Rickettsia parkeri, Rickettsia conorii, Rickettsia rickettsii, and over 20 other species throughout the world, uses the host-cell actin cytoskeleton to spread inter-and intracellularly. Similar to Listeria and Shigella, Rickettsia forms actin comet tails to propel its movement. However, the actin tails of Rickettsia consist of long and unbranched actin filaments, whereas those of Listeria and Shigella contain shorter and densely branched filaments (6, 7). These morphological differences stem from different molecular mechanisms for comet tail formation by these pathogens. Listeria and Shigella rely heavily on the activity of the host Arp2/3 complex that localizes uniformly along their tails (6). Although the Arp2/3 complex, activated by either host nucleation promoting factors (8) or the Rickettsia surface protein RickA (9, 10), is necessary for Rickettsia invasion (11), it is absent from Rickettsia tails (6). Another protein, Sca2 (surface cell antigen 2), has ...

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supporting

confidence: 84%

mentioning

confidence: 99%

Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism

Madasu

Suarez

Kast

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…They represent one of the major families of surfaceexposed proteins in Gram-negative bacteria and are organized in a modular fashion, i.e. a membrane-anchored C-terminal conserved domain that forms a trimeric abarrel pore (also called a-domain) and permits, through the type V protein secretion pathway (T5SS), the translocation of a passenger domain (stalk and an Nterminal head) to the bacterial cell surface (Dautin & Bernstein, 2007).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of DNA repeats in Burkholderia cenocepacia J2315 identifies a novel adhesin-like gene unique to epidemic-associated strains of the ET-12 lineage

2010

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Members of the Burkholderia cepacia complex (Bcc) are respiratory pathogens in patients with cystic fibrosis (CF). Close repetitive DNA sequences often associate with surface antigens to promote genetic variability in pathogenic bacteria. The genome of Burkholderia cenocepacia J2315, a CF isolate belonging to the epidemic lineage Edinburgh-Toronto (ET-12), was analysed for the presence of close repetitive DNA sequences. Among the 422 DNA close repeats, 45 genes potentially involved in virulence were identified and grouped into 12 classes; of these, 13 genes were included in the antigens class. Two trimeric autotransporter adhesins (TAA) among the 13 putative antigens are absent from the other Burkholderia genomes and are clustered downstream of the cci island that is a marker for transmissible B. cenocepacia strains. This cluster contains four adhesins, one outer-membrane protein, one sensor histidine kinase and two transcriptional regulators. By using PCR, we analysed three genes among 47 Bcc isolates to determine whether the cluster was conserved. These three genes were present in the isolates of the ET-12 lineage but absent in all the other members. Furthermore, the BCAM0224 gene was exclusively detected in this epidemic lineage and may serve as a valuable new addition to the field of Bcc diagnostics. The BCAM0224 gene encodes a putative TAA that demonstrates adhesive properties to the extracellular matrix protein collagen type I. Quantitative real-time PCR analysis indicated that BCAM0224 gene expression occurred preferentially for cells grown under high osmolarity, oxygen-limited conditions and oxidative stress. Inactivation of BCAM0224 in B. cenocepacia attenuates the ability of the mutant to promote cell adherence in vitro and impairs the overall bacterial virulence against Galleria mellonella as a model of infection. Together, our data show that BCAM0224 from B. cenocepacia J2315 represents a new collagen-binding TAA with no bacterial orthologues which has an important role in cellular adhesion and virulence.

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“…A range of methods have been used to address the folding state of autotransporters in their transit through the periplasm and initiation of assembly into the outer membrane [5][6][7][8] . Several lines of evidence indicate that a threading reaction enabling the passenger domain to emerge from the b-barrel can be completed after insertion into the outer membrane [8][9][10][11][12] .…”

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confidence: 99%

A mortise–tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes

et al. 2014

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Bacterial autotransporters comprise a 12-stranded membrane-embedded b-barrel domain, which must be folded in a process that entraps segments of an N-terminal passenger domain. This first stage of autotransporter folding determines whether subsequent translocation can deliver the N-terminal domain to its functional form on the bacterial cell surface. Here, paired glycine-aromatic 'mortise and tenon' motifs are shown to join neighbouring b-strands in the C-terminal barrel domain, and mutations within these motifs slow the rate and extent of passenger domain translocation to the surface of bacterial cells. In line with this, biophysical studies of the autotransporter Pet show that the conserved residues significantly quicken completion of the folding reaction and promote stability of the autotransporter barrel domain. Comparative genomics demonstrate conservation of glycine-aromatic residue pairings through evolution as a previously unrecognized feature of all autotransporter proteins.

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Protein Secretion in Gram-Negative Bacteria via the Autotransporter Pathway

Cited by 259 publications

References 97 publications

Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism

Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism

Genome-wide analysis of DNA repeats in Burkholderia cenocepacia J2315 identifies a novel adhesin-like gene unique to epidemic-associated strains of the ET-12 lineage

A mortise–tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes

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