scholarly journals Tandem Translation Generates a Chaperone for the Salmonella Type III Secretion System Protein SsaQ

2011 ◽  
Vol 286 (41) ◽  
pp. 36098-36107 ◽  
Author(s):  
Xiu-Jun Yu ◽  
Mei Liu ◽  
Steve Matthews ◽  
David W. Holden
Keyword(s):  
Type Iii Secretion ◽  
Ex Vivo ◽  
Eukaryotic Cell ◽  
Effector Proteins ◽  
Secretion Systems ◽  
Type Iii ◽  
Type Iii Secretion Systems ◽  
Function Loss ◽  
Bacterial Cytoplasm

Type III secretion systems (T3SSs) of bacterial pathogens involve the assembly of a surface-localized needle complex, through which translocon proteins are secreted to form a pore in the eukaryotic cell membrane. This enables the transfer of effector proteins from the bacterial cytoplasm to the host cell. A structure known as the C-ring is thought to have a crucial role in secretion by acting as a cytoplasmic sorting platform at the base of the T3SS. Here, we studied SsaQ, an FliN-like putative C-ring protein of the Salmonella pathogenicity island 2 (SPI-2)-encoded T3SS. ssaQ produces two proteins by tandem translation: a long form (SsaQL) composed of 322 amino acids and a shorter protein (SsaQS) comprising the C-terminal 106 residues of SsaQL. SsaQL is essential for SPI-2 T3SS function. Loss of SsaQS impairs the function of the T3SS both ex vivo and in vivo. SsaQS binds to its corresponding region within SsaQL and stabilizes the larger protein. Therefore, SsaQL function is optimized by a novel chaperone-like protein, produced by tandem translation from its own mRNA species.

scholarly journals Small-Molecule Type III Secretion System Inhibitors Block Assembly of the Shigella Type III Secreton

2008 ◽  
Vol 191 (2) ◽  
pp. 563-570 ◽  
Author(s):  
Andreas K. J. Veenendaal ◽  
Charlotta Sundin ◽  
Ariel J. Blocker
Keyword(s):  
Type Iii Secretion ◽  
Bacterial Infections ◽  
Shigella Flexneri ◽  
Effector Proteins ◽  
Host Cells ◽  
Incomplete Penetrance ◽  
Secretion Systems ◽  
Bacterial Surface ◽  
Type Iii ◽  
Type Iii Secretion Systems

ABSTRACT Type III secretion systems (T3SSs) are essential virulence devices for many gram-negative bacteria that are pathogenic for plants, animals, and humans. They serve to translocate virulence effector proteins directly into eukaryotic host cells. T3SSs are composed of a large cytoplasmic bulb and a transmembrane region into which a needle is embedded, protruding above the bacterial surface. The emerging antibiotic resistance of bacterial pathogens urges the development of novel strategies to fight bacterial infections. Therapeutics that rather than kill bacteria only attenuate their virulence may reduce the frequency or progress of resistance emergence. Recently, a group of salicylidene acylhydrazides were identified as inhibitors of T3SSs in Yersinia, Chlamydia, and Salmonella species. Here we show that these are also effective on the T3SS of Shigella flexneri, where they block all related forms of protein secretion so far known, as well as the epithelial cell invasion and induction of macrophage apoptosis usually demonstrated by this bacterium. Furthermore, we show the first evidence for the detrimental effect of these compounds on T3SS needle assembly, as demonstrated by increased numbers of T3S apparatuses without needles or with shorter needles. Therefore, the compounds generate a phenocopy of T3SS export apparatus mutants but with incomplete penetrance. We discuss why this would be sufficient to almost completely block the later secretion of effector proteins and how this begins to narrow the search for the molecular target of these compounds.

scholarly journals Bridging the Gap: Type III Secretion Systems in Plant-Beneficial Bacteria

2022 ◽  
Vol 10 (1) ◽  
pp. 187
Author(s):  
Antoine Zboralski ◽  
Adrien Biessy ◽  
Martin Filion
Keyword(s):  
Type Iii Secretion ◽  
Plant Pathogens ◽  
Plant Immunity ◽  
Effector Proteins ◽  
Secretion Systems ◽  
Beneficial Bacteria ◽  
Living Plant ◽  
Pseudomonas Spp ◽  
Type Iii ◽  
Type Iii Secretion Systems

Type III secretion systems (T3SSs) are bacterial membrane-embedded nanomachines translocating effector proteins into the cytoplasm of eukaryotic cells. They have been intensively studied for their important roles in animal and plant bacterial diseases. Over the past two decades, genome sequencing has unveiled their ubiquitous distribution in many taxa of Gram-negative bacteria, including plant-beneficial ones. Here, we discuss the distribution and functions of the T3SS in two agronomically important bacterial groups: the symbiotic nodule-forming nitrogen-fixing rhizobia and the free-living plant-beneficial Pseudomonas spp. In legume-rhizobia symbiosis, T3SSs and their cognate effectors play important roles, including the modulation of the plant immune response and the initiation of the nodulation process in some cases. In plant-beneficial Pseudomonas spp., the roles of T3SSs are not fully understood, but pertain to plant immunity suppression, biocontrol against eukaryotic plant pathogens, mycorrhization facilitation, and possibly resistance against protist predation. The diversity of T3SSs in plant-beneficial bacteria points to their important roles in multifarious interkingdom interactions in the rhizosphere. We argue that the gap in research on T3SSs in plant-beneficial bacteria must be bridged to better understand bacteria/eukaryotes rhizosphere interactions and to support the development of efficient plant-growth promoting microbial inoculants.

scholarly journals Evidence for Targeting of Yop Effectors by the Chromosomally Encoded Ysa Type III Secretion System of Yersinia enterocolitica

2002 ◽  
Vol 184 (20) ◽  
pp. 5563-5571 ◽  
Author(s):  
Briana M. Young ◽  
Glenn M. Young
Keyword(s):  
Yersinia Enterocolitica ◽  
Type Iii Secretion ◽  
Immunoblot Analysis ◽  
Effector Proteins ◽  
Secretion Systems ◽  
Necrosis Factor Alpha ◽  
Type Iii ◽  
Type Iii Secretion Systems ◽  
Molecular Masses ◽  
Factor Alpha

ABSTRACT Yersinia enterocolitica O:8 has two contact-dependent type III secretion systems (TTSSs). The Ysa TTSS is encoded by a set of genes located on the chromosome and exports Ysp proteins. The Ysc TTSS and the Yop effector proteins it exports are encoded by genes located on plasmid pYVe8081. In this study, secretion of YspG, YspH, and YspJ by the Ysa TTSS was shown to require pYVe8081. Furthermore, mutations that blocked the function of the Ysc TTSS did not affect YspG, YspH, and YspJ production. This indicated that YspG, YspH, and YspJ are encoded by genes located on pYVe8081 and that they may correspond to Yops. A comparison of Ysps with Yop effectors secreted by Y. enterocolitica indicated that YspG, YspH, and YspJ have apparent molecular masses similar to those of YopN, YopP, and YopE, respectively. Immunoblot analysis demonstrated that antibodies directed against YopN, YopP, and YopE recognized YspG, YspH, and YspJ. Furthermore, mutations in yopN, yopP, and yopE specifically blocked YopN, YopP, and YopE secretion by the Ysc TTSS and YspG, YspH, and YspJ secretion by the Ysa TTSS. These results indicate YspG, YspH, and YspJ are actually YopN, YopP, and YopE. Additional analysis demonstrated that YopP and YspH secretion was restored to yopP mutants by complementation in trans with a wild-type copy of the yopP gene. Examination of Y. enterocolitica-infected J774A.1 macrophages revealed that both the Ysc and Ysa TTSSs contribute to YopP-dependent suppression of tumor necrosis factor alpha production. This indicates that both the Ysa and Ysc TTSSs are capable of targeting YopP and that they influence Y. enterocolitica interactions with macrophages. Taken together, these results suggest that the Ysa and Ysc TTSSs contribute to Y. enterocolitica virulence by exporting both unique and common subsets of effectors.

scholarly journals Structural Insights of Shigella Translocator IpaB and Its Chaperone IpgC in Solution

2021 ◽  
Vol 11 ◽  
Author(s):  
Mariana L. Ferrari ◽  
Spyridoula N. Charova ◽  
Philippe J. Sansonetti ◽  
Efstratios Mylonas ◽  
Anastasia D. Gazi
Keyword(s):  
Host Cell ◽  
Type Iii Secretion ◽  
Secretion Systems ◽  
Host Cell Membrane ◽  
Type Iii ◽  
X Ray Scattering ◽  
Type Iii Secretion Systems ◽  
Key Factor ◽  
Bacterial Cytoplasm ◽  
Structural Insights

Bacterial Type III Secretion Systems (T3SSs) are specialized multicomponent nanomachines that mediate the transport of proteins either to extracellular locations or deliver Type III Secretion effectors directly into eukaryotic host cell cytoplasm. Shigella, the causing agent of bacillary dysentery or shigellosis, bears a set of T3SS proteins termed translocators that form a pore in the host cell membrane. IpaB, the major translocator of the system, is a key factor in promoting Shigella pathogenicity. Prior to secretion, IpaB is maintained inside the bacterial cytoplasm in a secretion competent folding state thanks to its cognate chaperone IpgC. IpgC couples T3SS activation to transcription of effector genes through its binding to MxiE, probably after the delivery of IpaB to the secretion export gate. Small Angle X-ray Scattering experiments and modeling reveal that IpgC is found in different oligomeric states in solution, as it forms a stable heterodimer with full-length IpaB in contrast to an aggregation-prone homodimer in the absence of the translocator. These results support a stoichiometry of interaction 1:1 in the IpgC/IpaB complex and the multi-functional nature of IpgC under different T3SS states.

scholarly journals Type III Secretion Systems and Disease

2007 ◽  
Vol 20 (4) ◽  
pp. 535-549 ◽  
Author(s):  
Bryan Coburn ◽  
Inna Sekirov ◽  
B. Brett Finlay
Keyword(s):  
Host Cell ◽  
Type Iii Secretion ◽  
Human Infection ◽  
Effector Proteins ◽  
Secretion Systems ◽  
Barrier Dysfunction ◽  
Type Iii ◽  
Extracellular Milieu ◽  
Host Cell Cytoplasm ◽  
Type Iii Secretion Systems

SUMMARY Type III secretion systems (T3SSs) are complex bacterial structures that provide gram-negative pathogens with a unique virulence mechanism enabling them to inject bacterial effector proteins directly into the host cell cytoplasm, bypassing the extracellular milieu. Although the effector proteins vary among different T3SS pathogens, common pathogenic mechanisms emerge, including interference with the host cell cytoskeleton to promote attachment and invasion, interference with cellular trafficking processes, cytotoxicity and barrier dysfunction, and immune system subversion. The activity of the T3SSs correlates closely with infection progression and outcome, both in animal models and in human infection. Therefore, to facilitate patient care and improve outcomes, it is important to understand the T3SS-mediated virulence processes and to target T3SSs in therapeutic and prophylactic development efforts.

scholarly journals MxiM and MxiJ, Base Elements of the Mxi-Spa Type III Secretion System of Shigella, Interact with and Stabilize the MxiD Secretin in the Cell Envelope

2001 ◽  
Vol 183 (24) ◽  
pp. 6991-6998 ◽  
Author(s):  
Raymond Schuch ◽  
Anthony T. Maurelli
Keyword(s):  
Cell Surface ◽  
Type Iii Secretion ◽  
Cell Envelope ◽  
General Structure ◽  
Eukaryotic Cell ◽  
Effector Proteins ◽  
Complex Assembly ◽  
Base Element ◽  
Type Iii

ABSTRACT The type III secretion pathway is broadly distributed across many parasitic bacterial genera and serves as a mechanism for delivering effector proteins to eukaryotic cell surface and cytosolic targets. While the effectors, as well as the host responses elicited, differ among type III systems, they all utilize a conserved set of 9 to 11 proteins that together form a bacterial envelope-associated secretory organelle or needle complex. The general structure of the needle complex consists of a transenvelope base containing at least three ring-forming proteins (MxiD, MxiJ, and MxiG in Shigella) that is connected to a hollow needle-like extension that projects away from the cell surface. Several studies have shown that the initial steps in needle complex assembly require interactions among the base proteins, although specific details of this process remain unknown. Here we identify a role for another base element inShigella, MxiM, in interactions with the major outer-membrane-associated ring-forming protein, MxiD. MxiM affects several features of MxiD, including its stability, envelope association, and assembly into homomultimeric structures. Interestingly, many of the effects were also elicited by the inner-membrane-associated base element, MxiJ. We confirmed that MxiM-MxiD and MxiJ-MxiD interactions occur in vivo in the cell envelope, and we present evidence that together these base elements can form a transmembrane structure which is likely an important intermediary in the process of needle complex assembly.

scholarly journals Analysis of the Contribution of Salmonella Pathogenicity Islands 1 and 2 to Enteric Disease Progression Using a Novel Bovine Ileal Loop Model and a Murine Model of Infectious Enterocolitis

2005 ◽  
Vol 73 (11) ◽  
pp. 7161-7169 ◽  
Author(s):  
Brian K. Coombes ◽  
Bryan A. Coburn ◽  
Andrew A. Potter ◽  
Susantha Gomis ◽  
Kuldip Mirakhur ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Disease Process ◽  
Loop Model ◽  
Enteric Disease ◽  
Wild Type ◽  
Secretion Systems ◽  
Ileal Loop ◽  
Type Iii ◽  
Type Iii Secretion Systems

ABSTRACT We have developed a novel ileal loop model for use in calves to analyze the contribution of Salmonella enterica serovar Typhimurium type III secretion systems to disease processes in vivo. Our model involves constructing ileal loops with end-to-end anastamoses to restore the patency of the small intestine, thereby allowing experimental animals to convalesce following surgery for the desired number of days. This model overcomes the time constraint imposed by ligated ileal loop models that have precluded investigation of Salmonella virulence factors during later stages of the infection process. Here, we have used this model to examine the enteric disease process at 24 h and 5 days following infection with wild-type Salmonella and mutants lacking the virulence-associated Salmonella pathogenicity island 1 (SPI-1) or SPI-2 type III secretion systems. We show that SPI-2 mutants are dramatically attenuated at 5 days following infection and report a new phenotype for SPI-1 mutants, which induce intestinal pathology in calves similar to wild-type Salmonella in the 5-day ileal loop model. Both of these temporal phenotypes for SPI-1 and SPI-2 mutants were corroborated in a second animal model of enteric disease using streptomycin-pretreated mice. These data delineate novel phenotypes for SPI-1 and SPI-2 mutants in the intestinal phase of bovine and murine salmonellosis and provide working models to further investigate the effector contribution to these pathologies.

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