Assembly of the type II secretion system

Howard, S. Peter

doi:10.1016/j.resmic.2013.03.018

Cited by 12 publications

(10 citation statements)

References 87 publications

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“…Thus, during T2S, protein substrates present in the periplasm are delivered to the T2S apparatus, presumably following their recognition by T2S C and T2S D (17), and then using energy generated at the IM, the pseudopilus acts as a piston or an Archimedes screw to push the proteins through the OM secretin (2). Although recent papers have detailed the structure of the T2S apparatus and the molecular mechanism of secretion (11)(12)(13)(14)(15), it has been some time since there was a review focused on the prevalence of T2S and its role in pathogenesis. Hence, this minireview will provide an update on the types of bacteria and pathogens that have T2S, the numbers and kinds of proteins that are secreted via T2S, and how T2S-dependent proteins promote infection.…”

mentioning

confidence: 99%

Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond

2017

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Type II secretion (T2S) is one means by which Gram-negative pathogens secrete proteins into the extracellular milieu and/or host organisms. Based upon recent genome sequencing, it is clear that T2S is largely restricted to the Proteobacteria, occurring in many, but not all, genera in the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Deltaproteobacteria classes. Prominent human and/or animal pathogens that express a T2S system(s) include Acinetobacter baumannii, Burkholderia pseudomallei, Chlamydia trachomatis, Escherichia coli, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Vibrio cholerae, and Yersinia enterocolitica. T2S-expressing plant pathogens include Dickeya dadantii, Erwinia amylovora, Pectobacterium carotovorum, Ralstonia solanacearum, Xanthomonas campestris, Xanthomonas oryzae, and Xylella fastidiosa. T2S also occurs in nonpathogenic bacteria, facilitating symbioses, among other things. The output of a T2S system can range from only one to dozens of secreted proteins, encompassing a diverse array of toxins, degradative enzymes, and other effectors, including novel proteins. Pathogenic processes mediated by T2S include the death of host cells, degradation of tissue, suppression of innate immunity, adherence to host surfaces, biofilm formation, invasion into and growth within host cells, nutrient assimilation, and alterations in host ion flux. The reach of T2S is perhaps best illustrated by those bacteria that clearly use it for both environmental survival and virulence; e.g., L. pneumophila employs T2S for infection of amoebae, growth within lung cells, dampening of cytokines, and tissue destruction. This minireview provides an update on the types of bacteria that have T2S, the kinds of proteins that are secreted via T2S, and how T2S substrates promote infection.KEYWORDS Legionella, T2S, type II secretion, Vibrio, animal pathogens, degradative enzymes, human pathogens, plant pathogens, toxins S ecreted proteins have a major role in the pathogenesis of bacterial infections, including important diseases of humans, animals, and plants. In the case of Gramnegative bacteria, there are seven secretion systems (types I, II, III, IV, V, VI, and IX) that mediate the export of "effector" proteins out of the bacterial cell and into the extracellular milieu or into target host cells (1-3). Type II secretion (T2S) was the first such system to be defined, based upon work done in the mid-1980s on pullulanase secretion by Klebsiella oxytoca (4). Further insight into T2S was then gained from the examination of Aeromonas, Pseudomonas, Vibrio, and a few additional members of the gammaproteobacteria (5, 6). Thus, T2S is considered a two-step process; i.e., proteins to be secreted are first carried across the inner membrane (IM) and into the periplasm by the Sec translocon (7) or Tat pathway (8) and then, after folding into a tertiary conformation (and in some instances, undergoing oligomerization), are transported across the outer membrane (...

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confidence: 99%

Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond

2017

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“…[13]. Eight of the mutations were in the N0 [1], N1 [3], N2 [3], and N3 [1] N-terminal sub-domains (Table 3), while the other three insertions were located in the C-terminal portion of ExeD and were not analyzed further.…”

Section: Resultsmentioning

confidence: 99%

“…Mutation of several conserved amino acids in the peptidoglycan binding domain of ExeA has also shown that the interaction with peptidoglycan is required for assembly of ExeD [23]. These results suggest that the ExeAB complex may be chaperoning the secretin through the cell wall, or may be required for assembly of the secretin within both the peptidoglycan layer and the outer membrane, as suggested by the size of this and other secretins that appear to completely cross the periplasm [1], [25]. Like ExeA, ExeB is absolutely required for assembly of ExeD, however, ExeB has no known functional domains and its role in secretin assembly is unknown [19], [20].…”

Section: Introductionmentioning

confidence: 89%

“…The secretion of enzymes and exotoxins by the type two secretion system (T2SS) is a widespread virulence mechanism of Gram negative bacterial pathogens [1]–[4]. The T2SS is a large, trans-envelope apparatus composed of 12–16 proteins designated GspC-O, which are highly conserved, and GspAB and GspS, which are variably found among different bacterial species.…”

Section: Introductionmentioning

confidence: 99%

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Assembly of the Type Two Secretion System in Aeromonas hydrophila Involves Direct Interaction between the Periplasmic Domains of the Assembly Factor ExeB and the Secretin ExeD

Vanderlinde

Zhong

et al. 2014

PLoS ONE

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The type two secretion system is a large, trans-envelope apparatus that secretes toxins across the outer membrane of many Gram-negative bacteria. In Aeromonas hydrophila, ExeA interacts with peptidoglycan and forms a heteromultimeric complex with ExeB that is required for assembly of the ExeD secretin of the secretion system in the outer membrane. While the peptidoglycan-ExeAB (PG-AB) complex is required for ExeD assembly, the assembly mechanism remains unresolved. We analyzed protein-protein interactions to address the hypothesis that ExeD assembly in the outer membrane requires direct interaction with the PG-AB complex. Yeast and bacterial two hybrid analyses demonstrated an interaction between the periplasmic domains of ExeB and ExeD. Two-codon insertion mutagenesis of exeD disrupted lipase secretion, and immunoblotting of whole cells demonstrated significantly reduced secretin in mutant cells. Mapping of the two-codon insertions and deletion analysis showed that the ExeB-ExeD interaction involves the N0 and N1 subdomains of ExeD. Rotational anisotropy using the purified periplasmic domains of ExeB and ExeD determined that the apparent dissociation constant of the interaction is 1.19±0.16 µM. These results contribute important support for a putative mechanism by which the PG-AB complex facilitates assembly of ExeD through direct interaction between ExeB and ExeD. Furthermore, our results provide novel insight into the assembly function of ExeB that may contribute to elucidating the role of homologous proteins in secretion of toxins from other Gram negative pathogens.

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“…Elucidating the mechanism of T2SS secretin assembly in the outer membrane has been a major focus of research; however, current models do not account for the structural barrier imposed by the PG sacculus in the cell envelope or for the size of the secretin in relation to the position of the PG in the periplasm (23,40). In A. hydrophila, assembly of the ExeD secretin requires the assembly factors ExeA and ExeB, components of the inner membrane ExeAB complex with a PG-binding domain in ExeA and an ExeD-binding domain in ExeB.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Peptidoglycan Cross-Linking Suppress the Secretin Assembly Defect Caused by Mutation of GspA in the Type II Secretion System

et al. 2017

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In Gram-negative bacteria, the peptidoglycan (PG) cell wall is a significant structural barrier for outer membrane protein assembly. In Aeromonas hydrophila, outer membrane multimerization of the type II secretion system (T2SS) secretin ExeD requires the function of the inner membrane assembly factor complex ExeAB. The putative mechanism of the complex involves the reorganization of PG and localization of ExeD, whereby ExeA functions by interacting with PG to form a site for secretin assembly and ExeB forms an interaction with ExeD. This mechanism led us to hypothesize that increasing the pore size of PG would circumvent the requirement for ExeA in the assembly of the ExeD secretin. Growth of A. hydrophila in 270 mM Gly reduced PG cross-links by approximately 30% and led to the suppression of secretin assembly defects in exeA strains and in those expressing ExeA mutants by enabling localization of the secretin in the outer membrane. We also established a heterologous ExeD assembly system in Escherichia coli and showed that ExeAB and ExeC are the only A. hydrophila proteins required for the assembly of the ExeD secretin in E. coli and that ExeAB-independent assembly of ExeD can occur upon overexpression of the D,D-carboxypeptidase PBP 5. These results support an assembly model in which, upon binding to PG, ExeA induces multimerization and pore formation in the sacculus, which enables ExeD monomers to interact with ExeB and assemble into a secretin that both is inserted in the outer membrane and crosses the PG layer to interact with the inner membrane platform of the T2SS. IMPORTANCEThe PG layer imposes a strict structural impediment for the assembly of macromolecular structures that span the cell envelope and serve as virulence factors in Gram-negative species. This work revealed that by decreasing PG crosslinking by growth in Gly, the absolute requirement for the PG-binding activity of ExeA in the assembly of the ExeD secretin was alleviated in A. hydrophila. In a heterologous assembly model in E. coli, expression of the carboxypeptidase PBP 5 could relieve the requirement for ExeAB in the assembly of the ExeD secretin. These results provide some mechanistic details of the ExeAB assembly complex function, in which the PG-binding and oligomerization functions of ExeAB are used to create a pore in the PG that is required for secretin assembly.KEYWORDS type II secretion system, peptidoglycan, secretin assembly T he secretion of protein toxins and enzymes via the type II secretion system (T2SS) is an important virulence mechanism as well as a major route of scavenging enzyme secretion and surface protein assembly for many Gram-negative bacteria (1-4). The T2SS is a large complex composed of 12 to 15 highly conserved proteins designated

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Assembly of the type II secretion system

Cited by 12 publications

References 87 publications

Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond

Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond

Assembly of the Type Two Secretion System in Aeromonas hydrophila Involves Direct Interaction between the Periplasmic Domains of the Assembly Factor ExeB and the Secretin ExeD

Alterations in Peptidoglycan Cross-Linking Suppress the Secretin Assembly Defect Caused by Mutation of GspA in the Type II Secretion System

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