Pilus Biogenesis via the Chaperone/Usher Pathway: An Integration of Structure and Function

Hung, Danielle L.; Hultgren, Scott J.

doi:10.1006/jsbi.1998.4049

Cited by 56 publications

(43 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the ability of RovA to bind to both the psaA and psaE promoter regions (7). It is also noteworthy that the pH 6 antigen belongs to a class of adhesins whose biogenesis follows the chaperone/ usher pathway (34). Interestingly, E. coli P pilus subunits misassembled in the periplasm by a prototypic chaperone/usher pathway trigger an ECS response perceived by the Cpx pathway (35,41).…”

Section: Discussionsupporting

confidence: 71%

Influence of the Cpx Extracytoplasmic-Stress-Responsive Pathway on Yersinia sp.-Eukaryotic Cell Contact

et al. 2007

View full text Add to dashboard Cite

The extracytoplasmic-stress-responsive CpxRA two-component signal transduction pathway allows bacteria to adapt to growth in extreme environments. It controls the production of periplasmic protein folding and degradation factors, which aids in the biogenesis of multicomponent virulence determinants that span the bacterial envelope. This is true of the Yersinia pseudotuberculosis Ysc-Yop type III secretion system. However, despite using a second-site suppressor mutation to restore Yop effector secretion by yersiniae defective in the CpxA sensor kinase, these bacteria poorly translocated Yops into target eukaryotic cells. Investigation of this phenotype herein revealed that the expression of genes which encode several surface-located adhesins is also influenced by the Cpx pathway. In particular, the expression and surface localization of invasin, an adhesin that engages ␤1-integrins on the eukaryotic cell surface, are severely restricted by the removal of CpxA. This reduces bacterial association with eukaryotic cells, which could be suppressed by the ectopic production of CpxA, invasin, or RovA, a positive activator of inv expression. In turn, these infected eukaryotic cells then became susceptible to intoxication by translocated Yop effectors. In contrast, bacteria harboring an in-frame deletion of cpxR, which encodes the cognate response regulator, displayed an enhanced ability to interact with cell monolayers, as well as elevated inv and rovA transcription. This phenotype could be drastically suppressed by providing a wild-type copy of cpxR in trans. We propose a mechanism of inv regulation influenced by the direct negative effects of phosphorylated CpxR on inv and rovA transcription. In this fashion, sensing of extracytoplasmic stress by CpxAR contributes to productive Yersinia sp.-eukaryotic cell interactions.

show abstract

Section: Discussionsupporting

confidence: 71%

Influence of the Cpx Extracytoplasmic-Stress-Responsive Pathway on Yersinia sp.-Eukaryotic Cell Contact

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Fimbrial adhesins such as the prototypical type 1 fimbriae of Escherichia coli are composed primarily of a major repeating subunit protein and often contain minor-subunit proteins (including the adhesin) at the tip of the organelle. The biogenesis of these fimbriae is dependent on a highly conserved chaperone-usher system (20,29). Nonfimbrial adhesins are a second class of adherence factors and encompass a diverse range of adhesins that includes the autotransporter (AT) family of proteins.…”

mentioning

confidence: 99%

UpaG, a New Member of the Trimeric Autotransporter Family of Adhesins in UropathogenicEscherichia coli

et al. 2008

View full text Add to dashboard Cite

The ability of Escherichia coli to colonize both intestinal and extraintestinal sites is driven by the presence of specific virulence factors, among which are the autotransporter (AT) proteins. Members of the trimeric AT adhesin family are important virulence factors for several gram-negative pathogens and mediate adherence to eukaryotic cells and extracellular matrix (ECM) proteins. In this study, we characterized a new trimeric AT adhesin (UpaG) from uropathogenic E. coli (UPEC). Molecular analysis of UpaG revealed that it is translocated to the cell surface and adopts a multimeric conformation. We demonstrated that UpaG is able to promote cell aggregation and biofilm formation on abiotic surfaces in CFT073 and various UPEC strains. In addition, UpaG expression resulted in the adhesion of CFT073 to human bladder epithelial cells, with specific affinity to fibronectin and laminin. Prevalence analysis revealed that upaG is strongly associated with E. coli strains from the B2 and D phylogenetic groups, while deletion of upaG had no significant effect on the ability of CFT073 to colonize the mouse urinary tract. Thus, UpaG is a novel trimeric AT adhesin from E. coli that mediates aggregation, biofilm formation, and adhesion to various ECM proteins.Pathogenic bacteria often interact with their host through surface proteins referred to as adhesins. Two major classes of adhesins have been described, and both utilize vastly different mechanisms for their assembly at the cell surface. Fimbrial adhesins such as the prototypical type 1 fimbriae of Escherichia coli are composed primarily of a major repeating subunit protein and often contain minor-subunit proteins (including the adhesin) at the tip of the organelle. The biogenesis of these fimbriae is dependent on a highly conserved chaperone-usher system (20,29). Nonfimbrial adhesins are a second class of adherence factors and encompass a diverse range of adhesins that includes the autotransporter (AT) family of proteins. AT proteins are particularly unique in that the information required for receptor recognition and routing and anchorage to the outer membrane is provided by the protein itself (25). Recent studies have identified a new group of nonfimbrial adhesins that have the capacity to form stable trimeric structures on the bacterial cell surface. These adhesins are characterized by a membrane-anchored C-terminal domain that forms a trimeric ␤-barrel pore and facilitates the translocation of a passenger domain (consisting of an extended stalk and an N-terminal head) to the bacterial cell surface via the type V secretion pathway (54, 67).Trimeric AT proteins have been identified from a range of different gram-negative bacterial pathogens. Where characterized, the function of trimeric AT proteins is universally associated with bacterial adherence, and thus they constitute an important group of virulence factors (14). The YadA adhesin from Yersinia enterocolitica represents the best-characterized trimeric AT protein. YadA mediates adherence to host epithelial cells an...

show abstract

“…An essential step in UPEC infection of the bladder is adherence to the host urothelial surface via type 1 pili (2,27,29). Type 1 pili are assembled via the chaperone/ usher pathway (3,30,53). They are adhesive hair-like fibers consisting of cylindrical pilus rods composed of FimA pilin subunits and small-tip fibrillae composed of FimF, FimG, and the adhesin FimH (6,31).…”

mentioning

confidence: 99%

Molecular Variations in Klebsiella pneumoniae and Escherichia coli FimH Affect Function and Pathogenesis in the Urinary Tract

et al. 2008

Self Cite

View full text Add to dashboard Cite

Type 1 pili mediate binding, invasion, and biofilm formation of uropathogenic Escherichia coli (UPEC) in the host urothelium during urinary tract infection (UTI) via the adhesin FimH. In this study, we characterized the molecular basis of functional differences between FimH of the UPEC isolate UTI89 and the Klebsiella pneumoniae cystitis isolate TOP52. Type 1 pili characteristically mediate mannose-sensitive hemagglutination of guinea pig erythrocytes. Although the adhesin domain of K. pneumoniae TOP52 FimH (FimH 52 ) is highly homologous to that of E. coli, with an identical mannose binding pocket and surrounding hydrophobic ridge, it lacks the ability to agglutinate guinea pig erythrocytes. In addition, FimH-dependent biofilm formation in K. pneumoniae is inhibited by heptyl mannose, but not methyl mannose, suggesting the need for contacts outside of the mannose binding pocket. The binding specificity differences observed for FimH 52 resulted in significant functional differences seen in the pathogenesis of K. pneumoniae UTI compared to E. coli UTI. Infections in a murine model of UTI demonstrated that although the K. pneumoniae strain TOP52 required FimH 52 for invasion and IBC formation in the bladder, FimH 52 was not essential for early colonization. This work reveals that a limited amount of sequence variation between the FimH of E. coli and K. pneumoniae results in significant differences in function and ability to colonize the urinary tract.

show abstract

Pilus Biogenesis via the Chaperone/Usher Pathway: An Integration of Structure and Function

Cited by 56 publications

References 108 publications

Influence of the Cpx Extracytoplasmic-Stress-Responsive Pathway on Yersinia sp.-Eukaryotic Cell Contact

Influence of the Cpx Extracytoplasmic-Stress-Responsive Pathway on Yersinia sp.-Eukaryotic Cell Contact

UpaG, a New Member of the Trimeric Autotransporter Family of Adhesins in UropathogenicEscherichia coli

Molecular Variations in Klebsiella pneumoniae and Escherichia coli FimH Affect Function and Pathogenesis in the Urinary Tract

Contact Info

Product

Resources

About