Pili in Gram-negative and Gram-positive bacteria — structure, assembly and their role in disease

Proft, Thomas; Baker, Edward N.

doi:10.1007/s00018-008-8477-4

Cited by 454 publications

(432 citation statements)

References 180 publications

(187 reference statements)

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“…Like Gram-negative bacteria, many Gram-positive pathogens express pili on their surface (1-3). These structures have aroused great interest because of their direct roles in infection and pathogenesis and their importance as vaccine candidates (2,3). They also use covalent isopeptide (amide) bonds, both intermolecular and intramolecular, to give strength and stability, and thus present a new paradigm among protein polymers (4)(5)(6).…”

mentioning

confidence: 99%

The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds

Kang

Paterson

Gaspar

et al. 2009

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

104

166

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Cell-surface pili are important virulence factors that enable bacterial pathogens to adhere to specific host tissues and modulate host immune response. Relatively little is known about the structure of Gram-positive bacterial pili, which are built by the sortase-catalyzed covalent crosslinking of individual pilin proteins. Here we report the 1.6-Å resolution crystal structure of the shaft pilin component SpaA from Corynebacterium diphtheriae , revealing both common and unique features. The SpaA pilin comprises 3 tandem Ig-like domains, with characteristic folds related to those typically found in non-pilus adhesins. Whereas both the middle and the C-terminal domains contain an intramolecular Lys–Asn isopeptide bond, previously detected in the shaft pilins of Streptococcus pyogenes and Bacillus cereus , the middle Ig-like domain also harbors a calcium ion, and the C-terminal domain contains a disulfide bond. By mass spectrometry, we show that the SpaA monomers are cross-linked in the assembled pili by a Lys–Thr isopeptide bond, as predicted by previous genetic studies. Together, our results reveal that despite profound dissimilarities in primary sequences, the shaft pilins of Gram-positive pathogens have strikingly similar tertiary structures, suggesting a modular backbone construction, including stabilizing intermolecular and intramolecular isopeptide bonds.

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mentioning

confidence: 99%

The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds

Kang

Paterson

Gaspar

et al. 2009

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

104

166

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“…For example, WWE3 and OD1 genomes encode components for type-IV pili, including pilT for twitching motility and several predicted pilins 16 . The pili genes are homologous to type-IV pili genes sometimes involved in the uptake of environmental DNA 33,34 and may aid the cells in interorganism interactions and interacting with the environment 34 . TEM images recorded in the current study confirm the existence of these structures on cell surfaces, in some cases at high abundance levels.…”

Section: Discussionmentioning

confidence: 99%

Diverse uncultivated ultra-small bacterial cells in groundwater

et al. 2015

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Bacteria from phyla lacking cultivated representatives are widespread in natural systems and some have very small genomes. Here we test the hypothesis that these cells are small and thus might be enriched by filtration for coupled genomic and ultrastructural characterization. Metagenomic analysis of groundwater that passed through a B0.2-mm filter reveals a wide diversity of bacteria from the WWE3, OP11 and OD1 candidate phyla. Cryogenic transmission electron microscopy demonstrates that, despite morphological variation, cells consistently have small cell size (0.009 ± 0.002 mm 3 ). Ultrastructural features potentially related to cell and genome size minimization include tightly packed spirals inferred to be DNA, few densely packed ribosomes and a variety of pili-like structures that might enable inter-organism interactions that compensate for biosynthetic capacities inferred to be missing from genomic data. The results suggest that extremely small cell size is associated with these relatively common, yet little known organisms.

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“…Pili in Gram-negative bacteria are typically formed by noncovalent homopolymerization of major pilus subunit proteins (pilins) (32). Recently discovered pili in Gram-positive bacteria are formed by covalent polymerization of pilin subunits in a process that requires a specific sortase enzyme (33). The additive long axis dimensions for SasG modules of varying length (Table 1) suggest that the interdomain interfaces provide rigidity.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcal biofilm-forming protein has a contiguous rod-like structure

Gruszka

Wojdyla

Bingham

et al. 2012

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

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Staphylococcus aureus and Staphylococcus epidermidis form communities (called biofilms) on inserted medical devices, leading to infections that affect many millions of patients worldwide and cause substantial morbidity and mortality. As biofilms are resistant to antibiotics, device removal is often required to resolve the infection. Thus, there is a need for new therapeutic strategies and molecular data that might assist their development. Surface proteins S. aureus surface protein G (SasG) and accumulation-associated protein ( S. epidermidis ) promote biofilm formation through their “B” regions. B regions contain tandemly arrayed G5 domains interspersed with approximately 50 residue sequences (herein called E) and have been proposed to mediate intercellular accumulation through Zn 2+ -mediated homodimerization. Although E regions are predicted to be unstructured, SasG and accumulation-associated protein form extended fibrils on the bacterial surface. Here we report structures of E–G5 and G5–E–G5 from SasG and biophysical characteristics of single and multidomain fragments. E sequences fold cooperatively and form interlocking interfaces with G5 domains in a head-to-tail fashion, resulting in a contiguous, elongated, monomeric structure. E and G5 domains lack a compact hydrophobic core, and yet G5 domain and multidomain constructs have thermodynamic stabilities only slightly lower than globular proteins of similar size. Zn 2+ does not cause SasG domains to form dimers. The work reveals a paradigm for formation of fibrils on the 100-nm scale and suggests that biofilm accumulation occurs through a mechanism distinct from the “zinc zipper.” Finally, formation of two domains by each repeat (as in SasG) might reduce misfolding in proteins when the tandem arrangement of highly similar sequences is advantageous.

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Pili in Gram-negative and Gram-positive bacteria — structure, assembly and their role in disease

Cited by 454 publications

References 180 publications

The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds

The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds

Diverse uncultivated ultra-small bacterial cells in groundwater

Staphylococcal biofilm-forming protein has a contiguous rod-like structure

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