scholarly journals The Animal Pathogen-Like Type III Secretion System Is Required for the Intracellular Survival of Burkholderia mallei within J774.2 Macrophages

2006 ◽  
Vol 74 (7) ◽  
pp. 4349-4353 ◽  
Author(s):  
Wilson J. Ribot ◽  
Ricky L. Ulrich
Keyword(s):  
Type Iii Secretion ◽  
Protein Delivery ◽  
Actin Polymerization ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Burkholderia Mallei ◽  
Intracellular Growth ◽  
Type Iii ◽  
Membrane Protrusions ◽  
Cell Spread

ABSTRACT Burkholderia mallei is a highly infectious gram-negative pathogen and is the causative agent of human and animal glanders. By generating polar mutations (disruption of bsaQ and bsaZ) in the B. mallei ATCC 23344 animal pathogen-like type III secretion system (TTS), we demonstrate that this bacterial protein delivery system is required for intracellular growth of B. mallei in J774.2 cells, formation of macrophage membrane protrusions, actin polymerization, and phagosomal escape. These findings suggest that TTS plays a role in the intracellular trafficking of B. mallei and may facilitate cell-to-cell spread via actin-based motility.

scholarly journals Chlamydial Lytic Exit from Host Cells Is Plasmid Regulated

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Chunfu Yang ◽  
Tregei Starr ◽  
Lihua Song ◽  
John H. Carlson ◽  
Gail L. Sturdevant ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Actin Polymerization ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Cytoskeletal Proteins ◽  
Host Cells ◽  
Genetic Mechanism ◽  
Developmental Cycle ◽  
Obligate Intracellular ◽  
Type Iii

ABSTRACTChlamydia trachomatisis an obligate intracellular bacterium that is a globally important human pathogen. The chlamydial plasmid is an attenuating virulence factor, but the molecular basis for attenuation is not understood. Chlamydiae replicate within a membrane-bound vacuole termed an inclusion, where they undergo a biphasic developmental growth cycle and differentiate from noninfectious into infectious organisms. Late in the developmental cycle, the fragile chlamydia-laden inclusion retains its integrity by surrounding itself with scaffolds of host cytoskeletal proteins. The ability of chlamydiae to developmentally free themselves from this cytoskeleton network is a fundamental virulence trait of the pathogen. Here, we show that plasmidless chlamydiae are incapable of disrupting their cytoskeletal entrapment and remain intracellular as stable mature inclusions that support high numbers of infectious organisms. By using deletion mutants of the eight plasmid-carried genes (Δpgp1to Δpgp8), we show that Pgp4, a transcriptional regulator of multiple chromosomal genes, is required for exit. Exit of chlamydiae is dependent on protein synthesis and is inhibited by the compound C1, an inhibitor of the type III secretion system (T3S). Exit of plasmid-free and Δpgp4organisms, which failed to lyse infected cells, was rescued by latrunculin B, an inhibitor of actin polymerization. Our findings describe a genetic mechanism of chlamydial exit from host cells that is dependent on an unknownpgp4-regulated chromosomal T3S effector gene.IMPORTANCEChlamydia's obligate intracellular life style requires both entry into and exit from host cells. Virulence factors that function in exiting are unknown. The chlamydial inclusion is stabilized late in the infection cycle by F-actin. A prerequisite of chlamydial exit is its ability to disassemble actin from the inclusion. We show that chlamydial plasmid-free organisms, and also a plasmid gene protein 4 (pgp4) null mutant, do not disassociate actin from the inclusion and fail to exit cells. We further provide evidence that Pgp4-regulated exit is dependent on the chlamydial type III secretion system. This study is the first to define a genetic mechanism that functions in chlamydial lytic exit from host cells. The findings also have practical implications for understanding why plasmid-free chlamydiae are highly attenuated and have the ability to elicit robust protective immune responses.

scholarly journals Delivery of Heterologous Proteins, Enzymes, and Antigens via the Bacterial Type III Secretion System

2020 ◽  
Vol 8 (5) ◽  
pp. 777 ◽  
Author(s):  
Heather A. Pendergrass ◽  
Aaron E. May
Keyword(s):  
Type Iii Secretion ◽  
Protein Delivery ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Host Cells ◽  
Heterologous Proteins ◽  
Communication Tool ◽  
Type Iii ◽  
Heterologous Protein Secretion ◽  
Multimeric Protein

The Type III Secretion System (T3SS) is a multimeric protein complex composed of over 20 different proteins, utilized by Gram-negative bacteria to infect eukaryotic host cells. The T3SS has been implicated as a virulence factor by which pathogens cause infection and has recently been characterized as a communication tool between bacteria and plant cells in the rhizosphere. The T3SS has been repurposed to be used as a tool for the delivery of non-native or heterologous proteins to eukaryotic cells or the extracellular space for a variety of purposes, including drug discovery and drug delivery. This review covers the methodology of heterologous protein secretion as well as multiple cases of utilizing the T3SS to deliver heterologous proteins or artificial materials. The research covered in this review will serve to outline the scope and limitations of utilizing the T3SS as a tool for protein delivery.

scholarly journals IpaD Localizes to the Tip of the Type III Secretion System Needle of Shigella flexneri

2006 ◽  
Vol 74 (8) ◽  
pp. 4391-4400 ◽  
Author(s):  
Marianela Espina ◽  
Andrew J. Olive ◽  
Roma Kenjale ◽  
David S. Moore ◽  
S. Fernando Ausar ◽  
...  
Keyword(s):  
Host Cell ◽  
Type Iii Secretion ◽  
Actin Polymerization ◽  
Shigella Flexneri ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Erythrocyte Membranes ◽  
Host Cell Membrane ◽  
Type Iii ◽  
Surface Localization

ABSTRACT Shigella flexneri, the causative agent of shigellosis, is a gram-negative bacterial pathogen that initiates infection by invading cells within the colonic epithelium. Contact with host cell surfaces induces a rapid burst of protein secretion via the Shigella type III secretion system (TTSS). The first proteins secreted are IpaD, IpaB, and IpaC, with IpaB and IpaC being inserted into the host cell membrane to form a pore for translocating late effectors into the target cell cytoplasm. The resulting pathogen-host cross talk results in localized actin polymerization, membrane ruffling, and, ultimately, pathogen entry. IpaD is essential for host cell invasion, but its role in this process is just now coming to light. IpaD is a multifunctional protein that controls the secretion and presentation of IpaB and IpaC at the pathogen-host interface. We show here that antibodies recognizing the surface-exposed N terminus of IpaD neutralize Shigella's ability to promote pore formation in erythrocyte membranes. We further show that MxiH and IpaD colocalize on the bacterial surface. When TTSS needles were sheared from the Shigella surface, IpaD was found at only the needle tips. Consistent with this, IpaD localized to the exposed tips of needles that were still attached to the bacterium. Molecular analyses then showed that the IpaD C terminus is required for this surface localization and function. Furthermore, mutations that prevent IpaD surface localization also eliminate all IpaD-related functions. Thus, this study demonstrates that IpaD localizes to the TTSA needle tip, where it functions to control the secretion and proper insertion of translocators into host cell membranes.

scholarly journals Bioinformatic and Biochemical Evidence for the Identification of the Type III Secretion System Needle Protein of Chlamydia trachomatis

2007 ◽  
Vol 190 (5) ◽  
pp. 1680-1690 ◽  
Author(s):  
H. J. Betts ◽  
L. E. Twiggs ◽  
M. S. Sal ◽  
P. B. Wyrick ◽  
K. A. Fields
Keyword(s):  
Type Iii Secretion ◽  
Neutralizing Antibodies ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
System Component ◽  
Intracellular Growth ◽  
Subunit Protein ◽  
Type Iii ◽  
Essential Components ◽  
Needle Protein

ABSTRACT Chlamydia spp. express a functional type III secretion system (T3SS) necessary for pathogenesis and intracellular growth. However, certain essential components of the secretion apparatus have diverged to such a degree as to preclude their identification by standard homology searches of primary protein sequences. One example is the needle subunit protein. Electron micrographs indicate that chlamydiae possess needle filaments, and yet database searches fail to identify a SctF homologue. We used a bioinformatics approach to identify a likely needle subunit protein for Chlamydia. Experimental evidence indicates that this protein, designated CdsF, has properties consistent with it being the major needle subunit protein. CdsF is concentrated in the outer membrane of elementary bodies and is surface exposed as a component of an extracellular needle-like projection. During infection CdsF is detectible by indirect immunofluorescence in the inclusion membrane with a punctuate distribution adjacent to membrane-associated reticulate bodies. Biochemical cross-linking studies revealed that, like other SctF proteins, CdsF is able to polymerize into multisubunit complexes. Furthermore, we identified two chaperones for CdsF, termed CdsE and CdsG, which have many characteristics of the Pseudomonas spp. needle chaperones PscE and PscG, respectively. In aggregate, our data are consistent with CdsF representing at least one component of the extended Chlamydia T3SS injectisome. The identification of this secretion system component is essential for studies involving ectopic reconstitution of the Chlamydia T3SS. Moreover, we anticipate that CdsF could serve as an efficacious target for anti-Chlamydia neutralizing antibodies.

Protein Delivery by Pseudomonas Type III Secretion System: Ex Vivo Complementation of p67phox-Deficient Chronic Granulomatous Disease

2000 ◽  
Vol 275 (3) ◽  
pp. 854-858 ◽  
Author(s):  
Benoît Polack ◽  
Sabrina Vergnaud ◽  
Marie Hélène Paclet ◽  
Danièle Lamotte ◽  
Bertrand Toussaint ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Type Iii Secretion ◽  
Protein Delivery ◽  
Ex Vivo ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Granulomatous Disease ◽  
Type Iii
Sign in / Sign up

Export Citation Format

Share Document