Molecular architecture of Streptococcus pneumoniae TIGR4 pili

Hilleringmann, Markus; Ringler, Philippe; Müller, Shirley A.; Angelis, Gabriella De; Rappuoli, Rino; Ferlenghi, Ilaria; Engel, Andréas

doi:10.1038/emboj.2009.360

Cited by 98 publications

(131 citation statements)

References 45 publications

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“…However, because the linear fiber-like pili of Gram-positive bacteria lack quaternary-level organization (16), it remains largely unknown how these megadalton-scale structures address the mechanical challenges for sustained adhesion.…”

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confidence: 99%

CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks

Echelman

Alegre-Cebollada

Badilla

et al. 2016

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

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Pathogenic bacteria adhere despite severe mechanical perturbations induced by the host, such as coughing. In Gram-positive bacteria, extracellular protein appendages termed pili are necessary for adherence under mechanical stress. However, little is known about the behavior of Gram-positive pili under force. Here, we demonstrate a mechanism by which Gram-positive pili are able to dissipate mechanical energy through mechanical unfolding and refolding of isopeptide bond-delimited polypeptide loops present in Ig-type CnaA domains. Using single-molecule force spectroscopy, we find that these loops of the pilus subunit SpaA of the SpaA-type pilus from Corynebacterium diphtheriae and FimA of the type 2 pilus from Actinomyces oris unfold and extend at forces that are the highest yet reported for globular proteins. Loop refolding is limited by the hydrophobic collapse of the polypeptide and occurs in milliseconds. Remarkably, both SpaA and FimA initially refold to mechanically weaker intermediates that recover strength with time or ligand binding. Based on the high force extensibility, CnaA-containing pili can dissipate ∼28-fold as much energy compared with their inextensible counterparts before reaching forces sufficient to cleave covalent bonds. We propose that efficient mechanical energy dissipation is key for sustained bacterial attachment against mechanical perturbations.bacterial adhesion | mechanical stability | single-molecule force spectroscopy | Gram-positive pili | isopeptide bond B acterial infections of solid tissues begin with the attachment of bacteria to target surfaces. In many instances, bacteria adhere against forces that oppose such attachment: micturition in the genitourinary tract (1) or mucociliary flow in the respiratory tract (2), for example. In such environments, a completely immobile adherent bacterium experiences a drag force that can be approximated by Stokes law, F = 6·π·r·η·v, where r is the Stokes radius of the bacterium (∼0.5 μm), η is the viscosity of the fluid (in the respiratory mucus, 1-100 Pa·s −1 ) (3), and v is the velocity of the fluid surrounding the bacterium (Fig. 1A). Under normal mucociliary flow (1-100 μm·s −1 ) (4), forces on a single bacterium can exceed several nanonewtons. Such high forces are sufficient to cleave covalent bonds within the initial adherence structures (5), which would terminate attachment. Understanding how bacteria manage to remain attached under such strong mechanical perturbations is of fundamental interest and could identify new targets for antibiotic development.The initial interaction between bacteria and the host is mediated by micrometer-long adhesive structures termed pili or fimbriae (Fig. 1A). Due to their adhesive role, pili are virulence factors that contribute to the development of infections (6). Structurally, pili are polymers of tens to hundreds of subunits, termed shaft pilins, that are assembled in series and are presented at the extracellular surface, often with inclusion of minor pilins that can have adhesive properties (6). Remar...

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confidence: 99%

CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks

Echelman

Alegre-Cebollada

Badilla

et al. 2016

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

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“…In S. pneumoniae, the pilus backbone is formed by covalently associated RrgB units; microscopy efforts have indicated that the molecules are associated with a directionality, in which a noselike protrusion defines the polarity of the fiber (25). The crystal structure of RrgB, fitted into a cryo-EM map of the pilus, confirms this polarity (24,59).…”

Section: Discussionmentioning

confidence: 62%

“…The crystal structure of RrgB, fitted into a cryo-EM map of the pilus, confirms this polarity (24,59). Notably, RrgA and RrgC were suggested as being located at the extremities of the fiber, with RrgC at the base and RrgA at the free end (25). The structure of RrgA revealed a four-domain flexible molecule carrying a von Willebrand factor (VWF) domain capable of recognizing extracellular matrix components (26), whereas RrgB displayed a threedomain fold (24,59).…”

Section: Discussionmentioning

confidence: 68%

“…Cell fractionation, transmission electron microscopy, in vitro polymerization tests, and cell wall sorting signal domain swapping experiments have confirmed that covalently linked repeating units of RrgB form the S. pneumoniae pilus backbone whereas RrgA is present at the tip of the pilus (18, 20 -25). Notably, RrgA was shown to be able to recognize extracellular matrix elements in vitro, a finding confirmed by its three-dimensional structure, which revealed the presence of an integrin collagen-recognition domain (9,25,26). These elements thus collectively suggest that RrgA plays the role of pilus adhesin.…”

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confidence: 59%

“…In addition, deletion of the gene coding for the minor base pilin GBS52 from Streptococcus agalactiae significantly reduces bacterial adhesion to pulmonary epithelial cells, an effect confirmed by the ability of anti-GBS52 antibodies to inhibit epithelial cell adhesion in vitro (28). These observations, coupled to the fact that RrgC was shown to be located at the base of the pilus fiber, suggested that it could play the role of pilus anchor to the cell wall (25). Despite these advances, the three-dimensional fold of RrgC, as well as its mode of attachment to the pilus base and/or the cell wall, remained unknown, impeding a more detailed comprehension of streptococcal pilus architecture.…”

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confidence: 59%

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Structural Basis of Pilus Anchoring by the Ancillary Pilin RrgC of Streptococcus pneumoniae

Shaik

Maccagni

Tourcier

et al. 2014

Journal of Biological Chemistry

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Background: RrgC is a key component of the pneumococcal pilus, a virulence factor that plays an important role in pathogenesis. Results: RrgC folds into three independent domains and requires the housekeeping sortase for surface association. Conclusion: The rod-like structure of RrgC suggests that it stably bridges peptidoglycan and pilus fiber. Significance: A complete model of the pneumococcal pilus reveals a multidomain, flexible assembly.

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Pilins in gram‐positive bacteria: A structural perspective

Krishnan

2015

IUBMB Life

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Pilins or fimbrilins are a class of proteins found in bacterial surface pilus, a hair-like surface appendage. Both the Gramnegative and -positive bacteria produce pilins to assemble pili on their cell-surface for different purposes including adherence, twitching motility, conjugation, immunomodulation, biofilm formation, and electron transfer. Immunogenic properties of the pilins make them attractive vaccine candidates. The polymerized pilins play a key role in the initiation of host adhesion, which is a critical step for bacterial colonization and infection. Because of their key role in adhesion and exposure on the cell surface, targeting the pilins-mediated adhesion (anti-adhesion therapy) is also seen as a promising alternative approach for preventing and treating bacterial infections, one that may overcome their ever-increasing repertoires of resistance mechanisms. Individual pilins interact with each other non-covalently to assemble the pilus fiber with the help of associated proteins like chaperones and Usher in Gramnegative bacteria. In contrast, the pilins in Gram-positive bacteria often connect with each other covalently, with the help of sortases. Certain unique structural features present on the pilins distinguish them from one another across different bacterial strains, and these dictate their cellular targets and functions. While the structure of pilins has been extensively studied in Gram-negative pathogenic bacteria, the pilins in Gram-positive pathogenic bacteria have been in only during the last decade. Recently, the discovery of pilins in nonpathogenic bacteria, such as Lactobacillus rhamnosus GG, has received great attention, though traditionally the attention was on pathogenic bacteria. This review summarizes and discusses the current structural knowledge of pilins in Gram-positive bacteria with emphasis on those pilins which are sortase substrates. V C 2015 IUBMB Life, 67(7): [533][534][535][536][537][538][539][540][541][542][543] 2015

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Molecular architecture of Streptococcus pneumoniae TIGR4 pili

Cited by 98 publications

References 45 publications

CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks

CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks

Structural Basis of Pilus Anchoring by the Ancillary Pilin RrgC of Streptococcus pneumoniae

Pilins in gram‐positive bacteria: A structural perspective

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