Biogenesis and regulation of the Vibrio cholerae toxin-coregulated pilus: analogies to other virulence factor secretory systems

Kaufman, Melissa R.; Shaw, Carolyn E.; Jones, Ian D.; Taylor, Ronald K.

doi:10.1016/0378-1119(93)90588-t

Cited by 67 publications

(49 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pilin subunits are synthesized in the cytosol and transported across the inner membrane, most likely via the Sec machinery. These subunits remain anchored in the inner membrane by α1-N, where a dedicated transmembrane prepilin peptidase cleaves off the N-terminal leader sequence on the cytoplasmic side of the subunit, and adds a methyl group to the N-terminal residue [16][17][18]. The globular domain folds in the periplasm, and disulfide bond formation is catalyzed by an oxidoreductase enzyme [19,20].…”

Section: Molecular Motors Driving Pilus Assembly and Disassemblymentioning

confidence: 99%

Type IV pili: paradoxes in form and function

Craig

2008

Current Opinion in Structural Biology

246

260

View full text Add to dashboard Cite

Type IV pili are filaments on the surfaces of many Gram-negative bacteria that mediate an extraordinary array of functions, including adhesion, motility, microcolony formation and secretion of proteases and colonization factors. Their prominent display on the surfaces of many bacterial pathogens, their vital role in virulence, and their ability to elicit an immune response make Type IV pilus structures particularly relevant for study as targets for component vaccines and therapies. Structural studies of the pili and components of the pilus assembly apparatus have proven extremely challenging, but new approaches and methods have produced important breakthroughs that are advancing our understanding of pilus functions and their complex assembly mechanism. These structures provide insights into the biology of Type IV pili as well as that of the related bacterial secretion and archaeal flagellar systems. This review will summarize the most recent structural advances on Type IV pili and their assembly components and highlight their significance.Type IV pili are homopolymers of a 15-20 kDa pilin subunit that emanate from the surfaces of many Gram-negative bacteria and at least one Gram-positive organism. These filaments, which appear smooth and featureless by electron microscopy (EM), are 6-9 nm in diameter and several microns in length (Fig. 1). Beneath their plain façade lies an exquisite helical architecture that provides for strength, flexibility and a multitude of functions, including twitching and gliding motility, adhesion, immune escape, DNA uptake, biofilm formation, microcolony formation, secretion, phage transduction and signal transduction. Unlike other bacterial pili, which use as few as two proteins for assembly [1,2], Type IV pilus biogenesis requires a dozen or more proteins, many of which share sequence conservation among divergent species. Pili are assembled, and in some cases disassembled, rapidly using powerful molecular motors that hydrolyze ATP. The proteins involved in pilus biogenesis form a dynamic but poorly-defined complex that spans both bacterial membranes and the intervening periplasm. Our knowledge of Type IV pili presents several paradoxes: What type of molecular architecture yields such thin flexible filaments that can withstand stresses greater than 100 pN? How does a single filament design provide for such functional diversity? How does the assembly apparatus allow for rapid polymerization and depolymerization at a rate of more than 1000 subunits/second? This review will focus on the latest structural findings, which help to explain these paradoxes and advance our understanding of this remarkable biological machine.Type IV pilus assembly involves 12 or more proteins that in many cases are encoded within the same operon. Several key components are utilized in all Type IV pilus systems and are also found in Type II secretion and archaeal flagellar systems [3][4][5]. These are: the pilin subunit; an inner membrane prepilin peptidase that cleaves the N-terminal leader peptide; an ...

show abstract

Section: Molecular Motors Driving Pilus Assembly and Disassemblymentioning

confidence: 99%

Type IV pili: paradoxes in form and function

Craig

2008

Current Opinion in Structural Biology

246

260

View full text Add to dashboard Cite

show abstract

“…Other environmental stimuli apparently influence the ability of ToxR to activate the expression of the regulatory gene toxT. The toxT gene is located within the tcp operon (Kaufman et al, 1993) and, although its activation is dependent upon ToxR (DiRita et al, 1991), readthrough transcription from the most proximal promoter in the tcp operon by an autoregulatory feedback loop contributes to its steady-state expression (Brown and Taylor, 1995). In strains engineered to express toxT independently of ToxR from a constitutive promoter, the repression of the regulon is alleviated in the classical biotype at pH 8.5 and in the El Tor biotype when grown under normally nonpermissive expression conditions .…”

Section: Influence Of Environmental Stimuli On the Toxr Regulonmentioning

confidence: 99%

Control of the ToxR virulence regulon in Vibrio cholerae by environmental stimuli

Skorupski

Taylor

1997

Molecular Microbiology

Self Cite

224

187

View full text Add to dashboard Cite

SummaryMany bacterial pathogens regulate the expression of virulence genes in a co-ordinate manner in response to changes in the environment. For example, the human pathogen, Vibrio cholerae, possesses a virulence regulon composed of over 20 genes involved in colonization, toxin production and bacterial survival within the host, which are co-ordinately regulated by external stimuli, such as temperature, pH and osmolarity. Although the expression of the regulon is dependent upon the transcriptional activator ToxR, most of these genes are controlled by a second transcriptional activator, ToxT, which is itself positively regulated by ToxR. The mechanisms by which environmental stimuli influence the ToxR regulon are not yet understood, but ToxR-mediated control over the expression of toxT clearly plays a role. The recent finding that the global regulator cAMP-CRP also influences the expression of the ToxR regulon under various environmental conditions raises new issues regarding the pathways and mechanisms by which this regulation is achieved and indicates that multiple overlapping systems are involved.

show abstract

“…Their next closest relatives are XcpS (-50% identity/70% similarity) , and then PilC and XpsF (-30% identity/60% similarity) . TcpE (see Kaufman et al , 1993) and ComG-2 are more distantly related showing only -20% identity/50% similarity to each other and to other proteins.…”

Section: Other Inner Membrane Components (Pile-like Proteins)mentioning

confidence: 99%

Common components in the assembly of type 4 fimbriae, DNA transfer systems, filamentous phage and protein‐secretion apparatus: a general system for the formation of surface‐associated protein complexes

Hobbs

Mattick

1993

Molecular Microbiology

358

286

View full text Add to dashboard Cite

Summary The Pseudomonas aeruginosa genes pilB‐D and pilQ are necessary for the assembly of type 4 fimbriae. Homologues of these genes and of the subunit (pilin) gene have been described in various different bacterial species, but not always in association with type 4 fimbrial biosynthesis and function. Pil‐like proteins are also involved in protein secretion, DNA transfer by conjugation and transformation, and morphogenesis of filamentous bacteriophages. It seems likely that the Pil homologues function in the processing and export of proteins resembling type 4 fimbrial sub‐units, and in their organization into fimbrial‐like structures. These may either be true type 4 fimbriae, or components of protein complexes which act in the transport of macromolecules (DNA or protein) into or out of the cell. Some PilB‐like and PilQ‐like proteins are apparently also involved in the assembly of non‐type 4 polymeric structures (filamentous phage virions and conjugative pili). The diverse studies summarized in this review are providing insight into an extensive infrastructural system which appears to be utilized in the formation of a variety of cell surface‐associated complexes.

show abstract

Biogenesis and regulation of the Vibrio cholerae toxin-coregulated pilus: analogies to other virulence factor secretory systems

Cited by 67 publications

References 28 publications

Type IV pili: paradoxes in form and function

Type IV pili: paradoxes in form and function

Control of the ToxR virulence regulon in Vibrio cholerae by environmental stimuli

Common components in the assembly of type 4 fimbriae, DNA transfer systems, filamentous phage and protein‐secretion apparatus: a general system for the formation of surface‐associated protein complexes

Contact Info

Product

Resources

About