The chaperone/usher pathway: a major terminal branch of the general secretory pathway

doi:10.1016/S1369-5274(98)80015-5

Current Opinion in Microbiology

Volume 1, Issue 2, April 1998, Pages 223-231

https://doi.org/10.1016/S1369-5274(98)80015-5 Get rights and content

Abstract

Gram-negative bacteria assemble a variety of adhesive organelles on their surface, including the thread-like structures known as pili. Recent studies on pilus assembly by the chaperone/usher pathway have revealed new insights into the mechanisms of pilus subunit export into the periplasm and targeting to the outer membrane. Signaling events controlling pilus biogenesis have begun to emerge and investigations of the usher have yielded insights into pilus translocation across the outer membrane.

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Cited by (161)

Unveiling molecular interactions that stabilize bacterial adhesion pili
2022, Biophysical Journal
Citation Excerpt :
Many bacteria express micrometer-long surface fibers called adhesion pili (or fimbriae), which are key virulence factors that mediate host-pathogen interactions. For Gram-negative bacteria, adhesive pili class are most commonly assembled via the classical chaperone-usher (CU) pathway (1). P pili are an archetypal CU pilus encoded by the pap gene, which is significantly prevalent among strains of uropathogenic Escherichia coli (UPEC) that cause pyelonephritis (kidney inflammation) (2,3).
Adhesion pili assembled by the chaperone-usher pathway are superelastic helical filaments on the surface of bacteria, optimized for attachment to target cells. Here, we investigate the biophysical function and structural interactions that stabilize P pili from uropathogenic bacteria. Using optical tweezers, we measure P pilus subunit-subunit interaction dynamics and show that pilus compliance is contour-length dependent. Atomic details of subunit-subunit interactions of pili under tension are shown using steered molecular dynamics (sMD) simulations. sMD results also indicate that the N-terminal “staple” region of P pili, which provides interactions with pilins that are four and five subunits away, significantly stabilizes the helical filament structure. These data are consistent with previous structural data, and suggest that more layer-to-layer interactions could compensate for the lack of a staple in type 1 pili. This study informs our understanding of essential structural and dynamic features of adhesion pili, supporting the hypothesis that the function of pili is critically dependent on their structure and biophysical properties.
Donor strand sequence, rather than donor strand orientation, determines the stability and non-equilibrium folding of the type 1 pilus subunit FimA
2020, Journal of Biological Chemistry
FimA is the main structural subunit of adhesive type 1 pili from uropathogenic Escherichia coli strains. Up to 3000 copies of FimA assemble to the helical pilus rod through a mechanism termed donor strand complementation, in which the incomplete immunoglobulin-like fold of each FimA subunit is complemented by the N-terminal extension (Nte) of the next subunit. The Nte of FimA, which exhibits a pseudo-palindromic sequence, is inserted in an antiparallel orientation relative to the last β-strand of the preceding subunit in the pilus. The resulting subunit-subunit interactions are extraordinarily stable against dissociation and unfolding. Alternatively, FimA can fold to a self-complemented monomer with anti-apoptotic activity, in which the Nte inserts intramolecularly into the FimA core in the opposite, parallel orientation. The FimA monomers, however, show dramatically lower thermodynamic stability compared with FimA subunits in the assembled pilus. Using self-complemented FimA variants with reversed, pseudo-palindromic extensions, we demonstrate that the high stability of FimA polymers is primarily caused by the specific interactions between the side chains of the Nte residues and the FimA core and not by the antiparallel orientation of the donor strand alone. In addition, we demonstrate that nonequilibrium two-state folding, a hallmark of FimA with the Nte inserted in the pilus rod-like, antiparallel orientation, only depends on the identity of the inserted Nte side chains and not on Nte orientation.
Adhesive mechanism of different Salmonella fimbrial adhesins
2019, Microbial Pathogenesis
Citation Excerpt :
The CU assembly pathway has been studied in great detail among different assembly pathways [85]. The CU fimbriae biogenesis starts with the production of the subunits in the cytoplasm and their export through the inner membrane via the general secretory pathway (GSP) [9,86,87]. The GSP usually uses the SecYEG complex and proteins SecDF/YajC.
Salmonellosis is a serious threat to human and animal health. Salmonella adhesion to the host cell is an initial and most crucial step in the pathogenesis of salmonellosis. Many factors are involved in the adhesion process of Salmonella infection. Fimbriae are one of the most important factors in the adhesion of Salmonella. The Salmonella fimbriae are assembled in three types of assembly pathways: chaperon–usher, nucleation–precipitation, and type IV fimbriae. These assembly pathways lead to multiple types of fimbriae. Salmonella fimbriae bind to host cell receptors to initiate adhesion. So far, many receptors have been identified, such as Toll-like receptors. However, several receptors that may be involved in the adhesive mechanism of Salmonella fimbriae are still un-identified. This review aimed to summarize the types of Salmonella fimbriae produced by different assembly pathways and their role in adhesion. It also enlisted previously discovered receptors involved in adhesion. This review might help readers to develop a comprehensive understanding of Salmonella fimbriae, their role in adhesion, and recently developed strategies to counter Salmonella infection.
The Cryoelectron Microscopy Structure of the Type 1 Chaperone-Usher Pilus Rod
2017, Structure
Citation Excerpt :
Chaperone-usher pili are long, thin surface appendages displayed by many pathogenic Gram-negative bacteria (Thanassi et al., 1998).
Adhesive chaperone-usher pili are long, supramolecular protein fibers displayed on the surface of many bacterial pathogens. The type 1 and P pili of uropathogenic Escherichia coli (UPEC) play important roles during urinary tract colonization, mediating attachment to the bladder and kidney, respectively. The biomechanical properties of the helical pilus rods allow them to reversibly uncoil in response to flow-induced forces, allowing UPEC to retain a foothold in the unique and hostile environment of the urinary tract. Here we provide the 4.2-Å resolution cryo-EM structure of the type 1 pilus rod, which together with the previous P pilus rod structure rationalizes the remarkable “spring-like” properties of chaperone-usher pili. The cryo-EM structure of the type 1 pilus rod differs in its helical parameters from the structure determined previously by a hybrid approach. We provide evidence that these structural differences originate from different quaternary structures of pili assembled in vivo and in vitro.
Structure of a Chaperone-Usher Pilus Reveals the Molecular Basis of Rod Uncoiling
2016, Cell
Citation Excerpt :
Chaperone-usher (CU) pili are ubiquitous appendages displayed on the surface of bacterial pathogens (Thanassi et al., 1998).
Types 1 and P pili are prototypical bacterial cell-surface appendages playing essential roles in mediating adhesion of bacteria to the urinary tract. These pili, assembled by the chaperone-usher pathway, are polymers of pilus subunits assembling into two parts: a thin, short tip fibrillum at the top, mounted on a long pilus rod. The rod adopts a helical quaternary structure and is thought to play essential roles: its formation may drive pilus extrusion by preventing backsliding of the nascent growing pilus within the secretion pore; the rod also has striking spring-like properties, being able to uncoil and recoil depending on the intensity of shear forces generated by urine flow. Here, we present an atomic model of the P pilus generated from a 3.8 Å resolution cryo-electron microscopy reconstruction. This structure provides the molecular basis for the rod’s remarkable mechanical properties and illuminates its role in pilus secretion.
Factors Required for Adhesion of Salmonella enterica Serovar Typhimurium to Lactuca sativa (Lettuce)
2023, Microbiology Spectrum

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The chaperone/usher pathway: a major terminal branch of the general secretory pathway

Abstract

Cell

Proc Natl Acad Sci USA

Annu Rev Microbiol

Mol Microbiol

Trends Microbiol

Mol Microbiol

Bacterial adhesins and their assembly

The Gal α(1–4) Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract

Proc Natl Acad Sci USA

Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination

Science

Structural polymorphism of bacterial adhesion pili

Nature

P pili in uropathogenic E. coli are composite fibres with distinct fibrillar adhesive tips

Nature

Specificity of binding of a strain of uropathogenic Escherichia coli to Galα(1–4)Gal-containing glycosphingolipids

J Biol Chem

Initiation of assembly and association of the structural elements of a bacterial pilus depend on two specialized tip proteins

EMBO J

Chaperone-assisted assembly and molecular architecture of adhesive pili

Annu Rev Microbiol

Outer membrane PapC usher discriminately recognizes periplasmic chaperone-pilus subunit complexes

Proc Natl Acad Sci USA

Nucleotide sequence, regulation and functional analysis of the papC gene required for cell surface localization of Pap pili of uropathogenic Escherichia coli

Mol Microbiol

Structure, function, and assembly of adhesive P pili

Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobactericeae

Nature

A new locus, pilE required for the binding of type 1 piliated Escherichia coli to erythrocytes

FEMS Microbiol Lett

FimH adhesin of type 1 pili is assembled into a fibrillar tip structure is the Enterobacteriaceae

Proc Natl Acad Sci USA

FimH family of type 1 fimbrial adhesins: functional heterogeneity due to minor sequence variations among fimH genes

J Bacteriol

Localization of a domain in the FimH adhesin of Escherichia coli type 1 fimbriae capable of receptor recognition and use of a domain-specific antibody to confer protection against experimental urinary tract infection

J Clin Invest

Lesions in two Escherichia coli type 1 pilus genes alter pilus number and length without affecting receptor binding

J Bacteriol

FimC is a periplasmic PapD-like chaperone that directs assembly of type 1 pili in bacteria

Proc Natl Acad Sci USA

The fimD gene required for cell surface localization of Escherichia coli type 1 fimbriae

Mol Gen Genet

Crystal structure of chaperone protein PapD reveals an immunoglobulin fold

Nature

Structural basis of pilus subunit recognition by the PapD chaperone

Science

Molecular basis of two subfamilies of immunoglobulin-like chaperones

EMBO J

The chaperone-assisted membrane release and folding pathway is sensed by two signal transduction systems

EMBO J

PapD chaperone function in pilus biogenesis depends on oxidant and chaperone-like activities of DsbA

Proc Natl Acad Sci USA

The DegP and DegQ periplasmic endoproteases of Escherichia coli: specificity for cleavage sites and substrate conformation

J Bacteriol

Regulation of Escherichia coli cell envelope proteins involved in protein folding and degradation by the Cpx two-component system

Genes Dev

The sE and the Cpx signal transduction systems control the synthesis of periplasmic protein-folding systems in Escherichia coli

Genes Dev