Type III secretion systems: the bacterial flagellum and the injectisome

Diepold, Andreas; Armitage, Judith P.

doi:10.1098/rstb.2015.0020

Cited by 189 publications

(187 citation statements)

References 272 publications

(393 reference statements)

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“…Salmonella pathogenicity island 1 (SPI1) and Shigella T3SA belong to the Inv/Mxi-Spa family of T3SS (25), and accordingly, their proteins share a moderate degree of sequence similarity. Interestingly, although most Salmonella enterica serovar Typhimurium (Salmonella) reside within phagosomes, a significant number of Salmonella (∼15-20%) escape from nascent vacuoles to establish an intracytoplasmic replicative niche in epithelial cells in a SPI1 T3SS-dependent manner (15,26).…”

Section: A Single Component Of the Translocon Apparatus Mediates Phagmentioning

confidence: 99%

“…T3SSs have been divided into eight distinct families based on phylogenetic analyses (25). The Salmonella SPI1 and Shigella Mxi-Spa systems are the best characterized members of the Inv/Mxi-Spa family, which also includes T3SSs from Chromobacterium (Cpi-1), Yersinia (Ysa), and Burkholderia (Bsa).…”

Section: A Single Component Of the Translocon Apparatus Mediates Phagmentioning

confidence: 99%

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The type III secretion system apparatus determines the intracellular niche of bacterial pathogens

Reeves

Klein

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Upon entry into host cells, intracellular bacterial pathogens establish a variety of replicative niches. Although some remodel phagosomes, others rapidly escape into the cytosol of infected cells. Little is currently known regarding how professional intracytoplasmic pathogens, including Shigella, mediate phagosomal escape. Shigella, like many other Gram-negative bacterial pathogens, uses a type III secretion system to deliver multiple proteins, referred to as effectors, into host cells. Here, using an innovative reductionist-based approach, we demonstrate that the introduction of a functional Shigella type III secretion system, but none of its effectors, into a laboratory strain of Escherichia coli is sufficient to promote the efficient vacuole lysis and escape of the modified bacteria into the cytosol of epithelial cells. This establishes for the first time, to our knowledge, a direct physiologic role for the Shigella type III secretion apparatus (T3SA) in mediating phagosomal escape. Furthermore, although protein components of the T3SA share a moderate degree of structural and functional conservation across bacterial species, we show that vacuole lysis is not a common feature of T3SA, as an effectorless strain of Yersinia remains confined to phagosomes. Additionally, by exploiting the functional interchangeability of the translocator components of the T3SA of Shigella, Salmonella, and Chromobacterium, we demonstrate that a single protein component of the T3SA translocon—Shigella IpaC, Salmonella SipC, or Chromobacterium CipC—determines the fate of intracellular pathogens within both epithelial cells and macrophages. Thus, these findings have identified a likely paradigm by which the replicative niche of many intracellular bacterial pathogens is established.

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Section: A Single Component Of the Translocon Apparatus Mediates Phagmentioning

confidence: 99%

Section: A Single Component Of the Translocon Apparatus Mediates Phagmentioning

confidence: 99%

The type III secretion system apparatus determines the intracellular niche of bacterial pathogens

Reeves

Klein

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…A recent phylogenetic analysis revealed that the injectisome originated from an ancient flagellar system by an exaptation process, i.e., recruiting core components from a rotary engine used for bacterial propulsion into a machine employed for interkingdom protein transport (38). Among the components of these machineries that preserve an evolutionary footprint in their sequences are the export apparatus proteins EscR, EscS, EscT, EscU, and EscV (FliP, FliQ, FliR, FlhB, and FlhA, respectively, in the flagellum), the inner membrane ring protein EscJ (FliF), the cytosolic ATPase complex components EscL and EscN (FliH and FliI), and the C-ring major component EscQ (FliM and FliN) (39).…”

mentioning

confidence: 99%

Functional Characterization of EscK (Orf4), a Sorting Platform Component of the Enteropathogenic Escherichia coli Injectisome

et al. 2017

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The type III secretion system (T3SS) is a supramolecular machine used by many bacterial pathogens to translocate effector proteins directly into the eukaryotic host cell cytoplasm. Enteropathogenic Escherichia coli (EPEC) is an important cause of infantile diarrheal disease in underdeveloped countries. EPEC virulence relies on a T3SS encoded within a chromosomal pathogenicity island known as the locus of enterocyte effacement (LEE). In this work, we pursued the functional characterization of the LEE-encoded protein EscK (previously known as Orf4). We provide evidence indicating that EscK is crucial for efficient T3S and belongs to the SctK (OrgA/YscK/MxiK) protein family, whose members have been implicated in the formation of a sorting platform for secretion of T3S substrates. Bacterial fractionation studies showed that EscK localizes to the inner membrane independently of the presence of any other T3SS component. Combining yeast two-hybrid screening and pulldown assays, we identified an interaction between EscK and the C-ring/sorting platform component EscQ. Site-directed mutagenesis of conserved residues revealed amino acids that are critical for EscK function and for its interaction with EscQ. In addition, we found that T3S substrate overproduction is capable of compensating for the absence of EscK. Overall, our data suggest that EscK is a structural component of the EPEC T3SS sorting platform, playing a central role in the recruitment of T3S substrates for boosting the efficiency of the protein translocation process.IMPORTANCE The type III secretion system (T3SS) is an essential virulence determinant for enteropathogenic Escherichia coli (EPEC) colonization of intestinal epithelial cells. Multiple EPEC effector proteins are injected via the T3SS into enterocyte cells, leading to diarrheal disease. The T3SS is encoded within a genomic pathogenicity island termed the locus of enterocyte effacement (LEE). Here we unravel the function of EscK, a previously uncharacterized LEE-encoded protein. We show that EscK is central for T3SS biogenesis and function. EscK forms a protein complex with EscQ, the main component of the cytoplasmic sorting platform, serving as a docking site for T3S substrates. Our results provide a comprehensive functional analysis of an understudied component of T3SSs.

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“…flagellum | chaperones | assembly factors | NMR spectroscopy | type III secretion T he flagellum is the organelle that enables bacterial locomotion and is one of the most sophisticated protein machines (1)(2)(3)(4). Flagella organelles may act as virulence factors because motility is crucial for the action of pathogenic bacteria (5,6).…”

mentioning

confidence: 99%

Recognition and targeting mechanisms by chaperones in flagellum assembly and operation

Khanra

Rossi

Economou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The flagellum is a complex bacterial nanomachine that requires the proper assembly of several different proteins for its function. Dedicated chaperones are central in preventing aggregation or undesired interactions of flagellar proteins, including their targeting to the export gate. FliT is a key flagellar chaperone that binds to several flagellar proteins in the cytoplasm, including its cognate filament-capping protein FliD. We have determined the solution structure of the FliT chaperone in the free state and in complex with FliD and the flagellar ATPase FliI. FliT adopts a four-helix bundle and uses a hydrophobic surface formed by the first three helices to recognize its substrate proteins. We show that the fourth helix constitutes the binding site for FlhA, a membrane protein at the export gate. In the absence of a substrate protein FliT adopts an autoinhibited structure wherein both the binding sites for substrates and FlhA are occluded. Substrate binding to FliT activates the complex for FlhA binding and thus targeting of the chaperone-substrate complex to the export gate. The activation and targeting mechanisms reported for FliT appear to be shared among the other flagellar chaperones.flagellum | chaperones | assembly factors | NMR spectroscopy | type III secretion

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Type III secretion systems: the bacterial flagellum and the injectisome

Cited by 189 publications

References 272 publications

The type III secretion system apparatus determines the intracellular niche of bacterial pathogens

The type III secretion system apparatus determines the intracellular niche of bacterial pathogens

Functional Characterization of EscK (Orf4), a Sorting Platform Component of the Enteropathogenic Escherichia coli Injectisome

Recognition and targeting mechanisms by chaperones in flagellum assembly and operation

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