scholarly journals Structural modeling of the flagellum MS ring protein FliF reveals similarities to the type III secretion system and sporulation complex

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1718 ◽  
Author(s):  
Julien R. Bergeron
Keyword(s):  
Basal Body ◽  
Type Iii Secretion ◽  
Bacterial Species ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Primary Role ◽  
Bacterial Surface ◽  
Type Iii ◽  
C Terminus ◽  
Cytosolic Side

The flagellum is a large proteinaceous organelle found at the surface of many bacteria, whose primary role is to allow motility through the rotation of a long extracellular filament. It is an essential virulence factor in many pathogenic species, and is also a priming component in the formation of antibiotic-resistant biofilms. The flagellum consists of the export apparatus on the cytosolic side; the basal body and rotor, spanning the bacterial membrane(s) and periplasm; and the hook-filament, that protrudes away from the bacterial surface. Formation of the basal body MS ring region, constituted of multiple copies of the protein FliF, is one of the initial steps of flagellum assembly. However, the precise architecture of FliF is poorly understood. Here, I report a bioinformatics analysis of the FliF sequence from various bacterial species, suggesting that its periplasmic region is composed of three globular domains. The first two are homologous to that of the type III secretion system injectisome proteins SctJ, and the third possesses a similar fold to that of the sporulation complex component SpoIIIAG. I also describe thatChlamydiapossesses an unusual FliF protein, lacking part of the SctJ homology domain and the SpoIIIAG-like domain, and fused to the rotor component FliG at its C-terminus. Finally, I have combined the sequence analysis of FliF with the EM map of the MS ring, to propose the first atomic model for the FliF oligomer, suggesting that FliF is structurally akin to a fusion of the two injectisome components SctJ and SctD. These results further define the relationship between the flagellum, injectisome and sporulation complex, and will facilitate future structural characterization of the flagellum basal body.

scholarly journals Structural modeling of the flagellum MS ring protein FliF reveals similarities to the type III secretion system and sporulation complex

2015 ◽  
Author(s):  
Julien R. C. Bergeron
Keyword(s):  
Basal Body ◽  
Type Iii Secretion ◽  
Structural Model ◽  
Bacterial Species ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Globular Domain ◽  
Primary Role ◽  
Bacterial Flagellum ◽  
Type Iii

The flagellum is a large proteinaceous organelle found at the surface of many bacteria, whose primary role is to allow motility through the rotation of a long extracellular filament. It is an essential virulence factor in many pathogenic species, and is also a priming component in the formation of antibiotic-resistant biofilms. The flagellum consists of the export apparatus and stator in the cytosol; the basal body, spanning the bacterial membrane(s) and periplasm; and the hook-filament, that protrudes away from the bacterial surface. Assembly of the bacterial flagellum is initiated by the formation of the basal body MS ring region, constituted of multiple copies of the protein FliF. Here, I report an analysis of the FliF sequence from various bacterial species, demonstrating that its periplasmic region is composed of a domain homologuous to that of the type III secretion system proteins PrgK, and of a second globular domain that possesses a similar fold to that of the sporulation complex component SpoIIIAG. I also report a structural model for the FliF oligomer, based on knowledge of the PrgK oligomer. These results further emphasize the similarity between the flagellum, T3SS and sporulation complex, and will facilitate further structural studies.

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.

scholarly journals The Structures of SctK and SctD from Pseudomonas aeruginosa Reveal the Interface of the Type III Secretion System Basal Body and Sorting Platform

2020 ◽  
Vol 432 (24) ◽  
pp. 166693
Author(s):  
Meenakumari Muthuramalingam ◽  
Sean K. Whittier ◽  
Scott Lovell ◽  
Kevin P. Battaile ◽  
Shoichi Tachiyama ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Basal Body ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii

scholarly journals Piericidin A1 Blocks Yersinia Ysc Type III Secretion System Needle Assembly

mSphere ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Jessica M. Morgan ◽  
Miles C. Duncan ◽  
Kevin S. Johnson ◽  
Andreas Diepold ◽  
Hanh Lam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Human Pathogens ◽  
Content Type ◽  
Bacterial Surface ◽  
Type Iii ◽  
Animal Pathogens ◽  
Bacterial Type

ABSTRACT The bacterial type III secretion system (T3SS) is widely used by both human and animal pathogens to cause disease yet remains incompletely understood. Deciphering how some natural products, such as the microbial metabolite piericidin, inhibit type III secretion can provide important insight into how the T3SS functions or is regulated. Taking this approach, we investigated the ability of piericidin to block T3SS function in several human pathogens. Surprisingly, piericidin selectively inhibited the Ysc family T3SS in enteropathogenic Yersinia but did not affect the function of a different T3SS within the same species. Furthermore, piericidin specifically blocked the formation of T3SS needles on the bacterial surface without altering the localization of several other T3SS components or regulation of T3SS gene expression. These data show that piericidin targets a mechanism important for needle assembly that is unique to the Yersinia Ysc T3SS. The type III secretion system (T3SS) is a bacterial virulence factor expressed by dozens of Gram-negative pathogens but largely absent from commensals. The T3SS is an attractive target for antimicrobial agents that may disarm pathogenic bacteria while leaving commensal populations intact. We previously identified piericidin A1 as an inhibitor of the Ysc T3SS in Yersinia pseudotuberculosis. Piericidins were first discovered as inhibitors of complex I of the electron transport chain in mitochondria and some bacteria. However, we found that piericidin A1 did not alter Yersinia membrane potential or inhibit flagellar motility powered by the proton motive force, indicating that the piericidin mode of action against Yersinia type III secretion is independent of complex I. Instead, piericidin A1 reduced the number of T3SS needle complexes visible by fluorescence microscopy at the bacterial surface, preventing T3SS translocator and effector protein secretion. Furthermore, piericidin A1 decreased the abundance of higher-order YscF needle subunit complexes, suggesting that piericidin A1 blocks YscF needle assembly. While expression of T3SS components in Yersinia are positively regulated by active type III secretion, the block in secretion by piericidin A1 was not accompanied by a decrease in T3SS gene expression, indicating that piericidin A1 may target a T3SS regulatory circuit. However, piericidin A1 still inhibited effector protein secretion in the absence of the T3SS regulator YopK, YopD, or YopN. Surprisingly, while piericidin A1 also inhibited the Y. enterocolitica Ysc T3SS, it did not inhibit the SPI-1 family Ysa T3SS in Y. enterocolitica or the Ysc family T3SS in Pseudomonas aeruginosa. Together, these data indicate that piericidin A1 specifically inhibits Yersinia Ysc T3SS needle assembly. IMPORTANCE The bacterial type III secretion system (T3SS) is widely used by both human and animal pathogens to cause disease yet remains incompletely understood. Deciphering how some natural products, such as the microbial metabolite piericidin, inhibit type III secretion can provide important insight into how the T3SS functions or is regulated. Taking this approach, we investigated the ability of piericidin to block T3SS function in several human pathogens. Surprisingly, piericidin selectively inhibited the Ysc family T3SS in enteropathogenic Yersinia but did not affect the function of a different T3SS within the same species. Furthermore, piericidin specifically blocked the formation of T3SS needles on the bacterial surface without altering the localization of several other T3SS components or regulation of T3SS gene expression. These data show that piericidin targets a mechanism important for needle assembly that is unique to the Yersinia Ysc T3SS.

scholarly journals Robustness and the evolution of length control strategies in the type III secretion system and flagellar hook

2019 ◽  
Author(s):  
Maulik K. Nariya ◽  
Abhishek Mallela ◽  
Jack J. Shi ◽  
Eric J. Deeds
Keyword(s):  
Type Iii Secretion ◽  
Average Length ◽  
Control Strategies ◽  
Bacterial Species ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Control Mechanisms ◽  
Switching Mechanism ◽  
Type Iii ◽  
Trade Offs

AbstractBacteria construct many structures, like the flagellar hook and the type III secretion system, that aid in crucial processes such as locomotion and pathogenesis. Experimental work has suggested two competing mechanisms bacteria could use to regulate length in these structures: the “ruler” mechanism and the “substrate switching” mechanism. In this work, we constructed a mathematical model of length control based on the ruler mechanism, and found that the predictions of this model are consistent with experimental data not just for the scaling of the average length with the ruler protein length, but also the variance. Interestingly, we found that the ruler mechanism allows for the evolution of needles with large average lengths without the concomitant large increase in variance that occurs in the substrate switching mechanism. These findings shed new light on the trade-offs that may have lead to the evolution of different length control mechanisms in different bacterial species.

scholarly journals YscP and YscU Switch the Substrate Specificity of the Yersinia Type III Secretion System by Regulating Export of the Inner Rod Protein YscI

2008 ◽  
Vol 190 (12) ◽  
pp. 4252-4262 ◽  
Author(s):  
Sarah E. Wood ◽  
Jin Jin ◽  
Scott A. Lloyd
Keyword(s):  
Substrate Specificity ◽  
Type Iii Secretion ◽  
Critical Role ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Eukaryotic Cells ◽  
Bacterial Surface ◽  
Type Iii ◽  
Proper Length ◽  
Null Strain

ABSTRACT Pathogenic yersiniae utilize a type III secretion system to inject antihost factors, called Yops, directly into the cytosol of eukaryotic cells. The Yops are injected via a needle-like structure, comprising the YscF protein, on the bacterial surface. While the needle is being assembled, Yops cannot be secreted. YscP and YscU switch the substrate specificity of the secretion system to enable Yop export once the needle attains its proper length. Here, we demonstrate that the inner rod protein YscI plays a critical role in substrate specificity switching. We show that YscI is secreted by the type III secretion system and that YscI secretion by a yscP mutant is abnormally elevated. Furthermore, we show that mutations in the cytoplasmic domain of YscU reduce YscI secretion by the yscP null strain. We also demonstrate that mutants expressing one of three forms of YscI (those with mutations Q84A, L87A, and L96A) secrete substantial amounts of Yops yet exhibit severe defects in needle formation. In the absence of YscP, mutants with the same changes in YscI assemble needles but are unable to secrete Yops. Together, these results suggest that the formation of the inner rod, not the needle, is critical for substrate specificity switching and that YscP and YscU exert their effects on substrate export by controlling the secretion of YscI.

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

2016 ◽  
Vol 113 (17) ◽  
pp. 4794-4799 ◽  
Author(s):  
Juan Du ◽  
Analise Z. Reeves ◽  
Jessica A. Klein ◽  
Donna J. Twedt ◽  
Leigh A. Knodler ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Type Iii Secretion ◽  
Bacterial Pathogens ◽  
Bacterial Species ◽  
Type Iii Secretion System ◽  
Laboratory Strain ◽  
Secretion System ◽  
Host Cells ◽  
Moderate Degree ◽  
Type Iii

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, includingShigella, 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 functionalShigellatype III secretion system, but none of its effectors, into a laboratory strain ofEscherichia coliis 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 theShigellatype 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 ofYersiniaremains confined to phagosomes. Additionally, by exploiting the functional interchangeability of the translocator components of the T3SA ofShigella,Salmonella, andChromobacterium, we demonstrate that a single protein component of the T3SA translocon—ShigellaIpaC,SalmonellaSipC, orChromobacteriumCipC—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.

scholarly journals Edwardsiella tarda EscE (Orf13 Protein) Is a Type III Secretion System-Secreted Protein That Is Required for the Injection of Effectors, Secretion of Translocators, and Pathogenesis in Fish

2015 ◽  
Vol 84 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Jin Fang Lu ◽  
Wei Na Wang ◽  
Gai Ling Wang ◽  
He Zhang ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Bacterial Species ◽  
Lethal Dose ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Edwardsiella Tarda ◽  
Dependent Manner ◽  
Wild Type ◽  
Content Type ◽  
Type Iii

The type III secretion system (T3SS) ofEdwardsiella tardais crucial for its intracellular survival and pathogenesis in fish. Theorf13gene (escE) ofE. tardais located 84 nucleotides (nt) upstream ofesrCin the T3SS gene cluster. We found that EscE is secreted and translocated in a T3SS-dependent manner and that amino acids 2 to 15 in the N terminus were required for a completely functional T3SS inE. tarda. Deletion ofescEabolished the secretion of T3SS translocators, as well as the secretion and translocation of T3SS effectors, but did not influence their intracellular protein levels inE. tarda. Complementation of theescEmutant with a secretion-incompetent EscE derivative restored the secretion of translocators and effectors. Interestingly, the effectors that were secreted and translocated were positively correlated with the EscE protein level inE. tarda. TheescEmutant was attenuated in the blue gourami fish infection model, as its 50% lethal dose (LD50) increased to 4 times that of the wild type. The survival rate of theescEmutant-strain-infected fish was 69%, which was much higher than that of the fish infected with the wild-type bacteria (6%). Overall, EscE represents a secreted T3SS regulator that controls effector injection and translocator secretion, thus contributing toE. tardapathogenesis in fish. The homology of EscE within the T3SSs of other bacterial species suggests that the mechanism of secretion and translocation control used byE. tardamay be commonly used by other bacterial pathogens.

scholarly journals The Modular Structure of the Inner-Membrane Ring Component PrgK Facilitates Assembly of the Type III Secretion System Basal Body

Structure ◽  
2015 ◽  
Vol 23 (1) ◽  
pp. 161-172 ◽  
Author(s):  
Julien R.C. Bergeron ◽  
Liam J. Worrall ◽  
Soumya De ◽  
Nikolaos G. Sgourakis ◽  
Adrienne H. Cheung ◽  
...  
Keyword(s):  
Basal Body ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Modular Structure ◽  
Inner Membrane ◽  
Type Iii
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