scholarly journals A polymorphic helix of a Salmonella needle protein relays signals defining distinct steps in type III secretion

PLoS Biology ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. e3000351 ◽  
Author(s):  
Emily Z. Guo ◽  
Daniel C. Desrosiers ◽  
Jan Zalesak ◽  
James Tolchard ◽  
Mélanie Berbon ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Type Iii ◽  
Needle Protein

scholarly journals Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP/NLRC4 inflammasome

2017 ◽  
Vol 114 (50) ◽  
pp. 13242-13247 ◽  
Author(s):  
Valeria M. Reyes Ruiz ◽  
Jasmine Ramirez ◽  
Nawar Naseer ◽  
Nicole M. Palacio ◽  
Ingharan J. Siddarthan ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Bacterial Species ◽  
Type Iii Secretion System ◽  
Nucleotide Binding ◽  
Secretion System ◽  
Binding Domain ◽  
Leucine Rich Repeat ◽  
Nucleotide Binding Domain ◽  
Type Iii ◽  
Needle Protein

Inflammasomes are cytosolic multiprotein complexes that initiate host defense against bacterial pathogens by activating caspase-1–dependent cytokine secretion and cell death. In mice, specific nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs) activate the nucleotide-binding domain, leucine-rich repeat-containing family, CARD domain-containing protein 4 (NLRC4) inflammasome upon sensing components of the type III secretion system (T3SS) and flagellar apparatus. NAIP1 recognizes the T3SS needle protein, NAIP2 recognizes the T3SS inner rod protein, and NAIP5 and NAIP6 recognize flagellin. In contrast, humans encode a single functional NAIP, raising the question of whether human NAIP senses one or multiple bacterial ligands. Previous studies found that human NAIP detects both flagellin and the T3SS needle protein and suggested that the ability to detect both ligands was achieved by multiple isoforms encoded by the single humanNAIPgene. Here, we show that human NAIP also senses theSalmonellaTyphimurium T3SS inner rod protein PrgJ and that T3SS inner rod proteins from multiple bacterial species are also detected. Furthermore, we show that a single human NAIP isoform is capable of sensing the T3SS inner rod, needle, and flagellin. Our findings indicate that, in contrast to murine NAIPs, promiscuous recognition of multiple bacterial ligands is conferred by a single human NAIP.

Solution Structure of Monomeric BsaL, the Type III Secretion Needle Protein of Burkholderia pseudomallei

2006 ◽  
Vol 359 (2) ◽  
pp. 322-330 ◽  
Author(s):  
Lingling Zhang ◽  
Yu Wang ◽  
Wendy L. Picking ◽  
William D. Picking ◽  
Roberto N. De Guzman
Keyword(s):  
Type Iii Secretion ◽  
Burkholderia Pseudomallei ◽  
Solution Structure ◽  
Type Iii ◽  
Needle Protein

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.

scholarly journals Mutations in the Yersinia pseudotuberculosis Type III Secretion System Needle Protein, YscF, That Specifically Abrogate Effector Translocation into Host Cells

2006 ◽  
Vol 189 (1) ◽  
pp. 83-97 ◽  
Author(s):  
Alison J. Davis ◽  
Joan Mecsas
Keyword(s):  
Type Iii Secretion ◽  
Yersinia Pseudotuberculosis ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Host Cells ◽  
Type Iii ◽  
Multistep Process ◽  
Needle Structure ◽  
Needle Protein ◽  
Structural Parts

ABSTRACT The trafficking of effectors, termed Yops, from Yersinia spp. into host cells is a multistep process that requires the type III secretion system (TTSS). The TTSS has three main structural parts: a base, a needle, and a translocon, which work together to ensure the polarized movement of Yops directly from the bacterial cytosol into the host cell cytosol. To understand the interactions that take place at the interface between the tip of the TTSS needle and the translocon, we developed a screen to identify mutations in the needle protein YscF that separated its function in secretion from its role in translocation. We identified 25 translocation-defective (TD) yscF mutants, which fall into five phenotypic classes. Some classes exhibit aberrant needle structure and/or reduced levels of Yop secretion, consistent with known functions for YscF. Strikingly, two yscF TD classes formed needles and secreted Yops normally but displayed distinct translocation defects. Class I yscF TD mutants showed diminished pore formation, suggesting incomplete pore insertion and/or assembly. Class II yscF TD mutants formed pores but showed nonpolar translocation, suggesting unstable needle-translocon interactions. These results indicate that YscF functions in Yop secretion and translocation can be genetically separated. Furthermore, the identification of YscF residues that are required for the assembly of the translocon and/or productive interactions with the translocon has allowed us to initiate the mapping of the needle-translocon interface.

scholarly journals Cutting Edge: Mouse NAIP1 Detects the Type III Secretion System Needle Protein

2013 ◽  
Vol 191 (8) ◽  
pp. 3986-3989 ◽  
Author(s):  
Manira Rayamajhi ◽  
Daniel E. Zak ◽  
Joseph Chavarria-Smith ◽  
Russell E. Vance ◽  
Edward A. Miao
Keyword(s):  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Cutting Edge ◽  
Type Iii ◽  
Needle Protein

scholarly journals Mutations in the Pseudomonas aeruginosa Needle Protein GenepscFConfer Resistance to Phenoxyacetamide Inhibitors of the Type III Secretion System

2014 ◽  
Vol 58 (4) ◽  
pp. 2211-2220 ◽  
Author(s):  
Nicholas O. Bowlin ◽  
John D. Williams ◽  
Claire A. Knoten ◽  
Matthew C. Torhan ◽  
Tommy F. Tashjian ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Molecular Target ◽  
Secretion System ◽  
Host Cells ◽  
Content Type ◽  
Type Iii ◽  
Unknown Protein ◽  
Needle Protein

ABSTRACTThe type III secretion system (T3SS) is a clinically important virulence mechanism inPseudomonas aeruginosathat secretes and translocates effector toxins into host cells, impeding the host's rapid innate immune response to infection. Inhibitors of T3SS may be useful as prophylactic or adjunctive therapeutic agents to augment the activity of antibiotics inP. aeruginosainfections, such as pneumonia and bacteremia. One such inhibitor, the phenoxyacetamide MBX 1641, exhibits very responsive structure-activity relationships, including striking stereoselectivity, in its inhibition ofP. aeruginosaT3SS. These features suggest interaction with a specific, but unknown, protein target. Here, we identify the apparent molecular target by isolating inhibitor-resistant mutants and mapping the mutation sites by deep sequencing. Selection and sequencing of four independent mutants resistant to the phenoxyacetamide inhibitor MBX 2359 identified the T3SS genepscF, encoding the needle apparatus, as the only locus of mutations common to all four strains. Transfer of the wild-type and mutated alleles ofpscF, together with its chaperone and cochaperone genespscEandpscG, to a ΔpscF P. aeruginosastrain demonstrated that each of the single-codon mutations inpscFis necessary and sufficient to provide secretion and translocation that is resistant to a variety of phenoxyacetamide inhibitor analogs but not to T3SS inhibitors with different chemical scaffolds. These results implicate the PscF needle protein as an apparent new molecular target for T3SS inhibitor discovery and suggest that three other chemically distinct T3SS inhibitors interact with one or more different targets or a different region of PscF.

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