scholarly journals Biological Diversity of Prokaryotic Type IV Secretion Systems

2009 ◽  
Vol 73 (4) ◽  
pp. 775-808 ◽  
Author(s):  
Cristina E. Alvarez-Martinez ◽  
Peter J. Christie
Keyword(s):  
Target Cell ◽  
Biological Diversity ◽  
Cell Interaction ◽  
Type Iv Secretion ◽  
Target Cells ◽  
Secretion Systems ◽  
Extracellular Milieu ◽  
Type Iv ◽  
Type Iv Secretion Systems ◽  
Cell Envelopes

SUMMARY Type IV secretion systems (T4SS) translocate DNA and protein substrates across prokaryotic cell envelopes generally by a mechanism requiring direct contact with a target cell. Three types of T4SS have been described: (i) conjugation systems, operationally defined as machines that translocate DNA substrates intercellularly by a contact-dependent process; (ii) effector translocator systems, functioning to deliver proteins or other macromolecules to eukaryotic target cells; and (iii) DNA release/uptake systems, which translocate DNA to or from the extracellular milieu. Studies of a few paradigmatic systems, notably the conjugation systems of plasmids F, R388, RP4, and pKM101 and the Agrobacterium tumefaciens VirB/VirD4 system, have supplied important insights into the structure, function, and mechanism of action of type IV secretion machines. Information on these systems is updated, with emphasis on recent exciting structural advances. An underappreciated feature of T4SS, most notably of the conjugation subfamily, is that they are widely distributed among many species of gram-negative and -positive bacteria, wall-less bacteria, and the Archaea. Conjugation-mediated lateral gene transfer has shaped the genomes of most if not all prokaryotes over evolutionary time and also contributed in the short term to the dissemination of antibiotic resistance and other virulence traits among medically important pathogens. How have these machines adapted to function across envelopes of distantly related microorganisms? A survey of T4SS functioning in phylogenetically diverse species highlights the biological complexity of these translocation systems and identifies common mechanistic themes as well as novel adaptations for specialized purposes relating to the modulation of the donor-target cell interaction.

scholarly journals Two type IV secretion systems with different functions in Burkholderia cenocepacia K56-2

Microbiology ◽  
2009 ◽  
Vol 155 (12) ◽  
pp. 4005-4013 ◽  
Author(s):  
Ruifu Zhang ◽  
John J. LiPuma ◽  
Carlos F. Gonzalez
Keyword(s):  
Type Iv Secretion ◽  
Burkholderia Cenocepacia ◽  
Target Cells ◽  
Secretion Systems ◽  
Type Iv ◽  
Plasmid Mobilization ◽  
Type Iv Secretion Systems ◽  
Derivative Plasmid ◽  
Chromosome Ii ◽  
Bacterial Type

Bacterial type IV secretion systems (T4SS) perform two fundamental functions related to pathogenesis: the delivery of effector molecules to eukaryotic target cells, and genetic exchange. Two T4SSs have been identified in Burkholderia cenocepacia K56-2, a representative of the ET12 lineage of the B. cepacia complex (Bcc). The plant tissue watersoaking (Ptw) T4SS encoded on a resident 92 kb plasmid is a chimera composed of VirB/D4 and F-specific subunits, and is responsible for the translocation of effector(s) that have been linked to the Ptw phenotype. The bc-VirB/D4 system located on chromosome II displays homology to the VirB/D4 T4SS of Agrobacterium tumefaciens. In contrast to the Ptw T4SS, the bc-VirB/D4 T4SS was found to be dispensable for Ptw effector(s) secretion, but was found to be involved in plasmid mobilization. The fertility inhibitor Osa did not affect the secretion of Ptw effector(s) via the Ptw system, but did disrupt the mobilization of a RSF1010 derivative plasmid.

scholarly journals Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Carrie L. Shaffer ◽  
James A. D. Good ◽  
Santosh Kumar ◽  
K. Syam Krishnan ◽  
Jennifer A. Gaddy ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Small Molecules ◽  
Bacterial Pathogens ◽  
Effector Proteins ◽  
Type Iv Secretion ◽  
Target Cells ◽  
Effector Protein ◽  
Secretion Systems ◽  
Type Iv ◽  
H Pylori

ABSTRACT Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85) that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA) and peptidoglycan into gastric epithelial cells. In H. pylori , KSK85 impedes biogenesis of the pilus appendage associated with the cag T4SS, while C10 disrupts cag T4SS activity without perturbing pilus assembly. In addition to the effects in H. pylori , we demonstrate that these compounds disrupt interbacterial DNA transfer by conjugative T4SSs in Escherichia coli and impede vir T4SS-mediated DNA delivery by Agrobacterium tumefaciens in a plant model of infection. Of note, C10 effectively disarmed dissemination of a derepressed IncF plasmid into a recipient bacterial population, thus demonstrating the potential of these compounds in mitigating the spread of antibiotic resistance determinants driven by conjugation. To our knowledge, this study is the first report of synthetic small molecules that impair delivery of both effector protein and DNA cargos by diverse T4SSs. IMPORTANCE Many human and plant pathogens utilize complex nanomachines called type IV secretion systems (T4SSs) to transport proteins and DNA to target cells. In addition to delivery of harmful effector proteins into target cells, T4SSs can disseminate genetic determinants that confer antibiotic resistance among bacterial populations. In this study, we sought to identify compounds that disrupt T4SS-mediated processes. Using the human gastric pathogen H. pylori as a model system, we identified and characterized two small molecules that prevent transfer of an oncogenic effector protein to host cells. We discovered that these small molecules also prevented the spread of antibiotic resistance plasmids in E. coli populations and diminished the transfer of tumor-inducing DNA from the plant pathogen A. tumefaciens to target cells. Thus, these compounds are versatile molecular tools that can be used to study and disarm these important bacterial machines.

scholarly journals The structural biology of type IV secretion systems

2009 ◽  
Vol 7 (10) ◽  
pp. 703-714 ◽  
Author(s):  
Rémi Fronzes ◽  
Peter J. Christie ◽  
Gabriel Waksman
Keyword(s):  
Structural Biology ◽  
Type Iv Secretion ◽  
Secretion Systems ◽  
Type Iv ◽  
Type Iv Secretion Systems

scholarly journals T4SP Database 2.0: An Improved Database for Type IV Secretion Systems in Bacterial Genomes with New Online Analysis Tools

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Na Han ◽  
Weiwen Yu ◽  
Yujun Qiang ◽  
Wen Zhang
Keyword(s):  
Recipient Cell ◽  
Bacterial Species ◽  
Genetic Material ◽  
Type Iv Secretion ◽  
Bacterial Strains ◽  
Secretion Systems ◽  
Bacterial Genomes ◽  
Type Iv ◽  
Type Iv Secretion Systems ◽  
User Friendly

Type IV secretion system (T4SS) can mediate the passage of macromolecules across cellular membranes and is essential for virulent and genetic material exchange among bacterial species. The Type IV Secretion Project 2.0 (T4SP 2.0) database is an improved and extended version of the platform released in 2013 aimed at assisting with the detection of Type IV secretion systems (T4SS) in bacterial genomes. This advanced version provides users with web server tools for detecting the existence and variations of T4SS genes online. The new interface for the genome browser provides a user-friendly access to the most complete and accurate resource of T4SS gene information (e.g., gene number, name, type, position, sequence, related articles, and quick links to other webs). Currently, this online database includes T4SS information of 5239 bacterial strains.Conclusions. T4SS is one of the most versatile secretion systems necessary for the virulence and survival of bacteria and the secretion of protein and/or DNA substrates from a donor to a recipient cell. This database on virB/D genes of the T4SS system will help scientists worldwide to improve their knowledge on secretion systems and also identify potential pathogenic mechanisms of various microbial species.

scholarly journals Bacterial Type IV secretion systems: versatile virulence machines

2012 ◽  
Vol 7 (2) ◽  
pp. 241-257 ◽  
Author(s):  
Daniel E Voth ◽  
Laura J Broederdorf ◽  
Joseph G Graham
Keyword(s):  
Type Iv Secretion ◽  
Secretion Systems ◽  
Type Iv ◽  
Type Iv Secretion Systems ◽  
Bacterial Type
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