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Type I Secretion Systems—One Mechanism for All?

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  • Authors: Olivia Spitz1, Isabelle N. Erenburg2, Tobias Beer3, Kerstin Kanonenberg4, I. Barry Holland5, Lutz Schmitt6
  • Editors: Maria Sandkvist7, Eric Cascales8, Peter J. Christie9
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 2: Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 3: Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 4: Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 5: Institute of Genetics and Microbiology, University of Paris-Sud, Orsay, France; 6: Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 7: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan; 8: CNRS Aix-Marseille Université, Mediterranean Institute of Microbiology, Marseille, France; 9: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas
  • Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.PSIB-0003-2018
  • Received 20 August 2018 Accepted 15 January 2019 Published 08 March 2019
  • Lutz Schmitt, [email protected]
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  • Abstract:

    Type I secretion systems (T1SS) are widespread in Gram-negative bacteria, especially in pathogenic bacteria, and they secrete adhesins, iron-scavenger proteins, lipases, proteases, or pore-forming toxins in the unfolded state in one step across two membranes without any periplasmic intermediate into the extracellular space. The substrates of T1SS are in general characterized by a C-terminal secretion sequence and nonapeptide repeats, so-called GG repeats, located N terminal to the secretion sequence. These GG repeats bind Ca ions in the extracellular space, which triggers folding of the entire protein. Here we summarize our current knowledge of how Gram-negative bacteria secrete these substrates, which can possess a molecular mass of up to 1,500 kDa. We also describe recent findings that demonstrate that the absence of periplasmic intermediates, the “classic” mode of action, does not hold true for all T1SS and that we are beginning to realize modifications of a common theme.

  • Citation: Spitz O, Erenburg I, Beer T, Kanonenberg K, Holland I, Schmitt L. 2019. Type I Secretion Systems—One Mechanism for All?. Microbiol Spectrum 7(2):PSIB-0003-2018. doi:10.1128/microbiolspec.PSIB-0003-2018.

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/content/journal/microbiolspec/10.1128/microbiolspec.PSIB-0003-2018
2019-03-08
2019-08-19

Abstract:

Type I secretion systems (T1SS) are widespread in Gram-negative bacteria, especially in pathogenic bacteria, and they secrete adhesins, iron-scavenger proteins, lipases, proteases, or pore-forming toxins in the unfolded state in one step across two membranes without any periplasmic intermediate into the extracellular space. The substrates of T1SS are in general characterized by a C-terminal secretion sequence and nonapeptide repeats, so-called GG repeats, located N terminal to the secretion sequence. These GG repeats bind Ca ions in the extracellular space, which triggers folding of the entire protein. Here we summarize our current knowledge of how Gram-negative bacteria secrete these substrates, which can possess a molecular mass of up to 1,500 kDa. We also describe recent findings that demonstrate that the absence of periplasmic intermediates, the “classic” mode of action, does not hold true for all T1SS and that we are beginning to realize modifications of a common theme.

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Image of FIGURE 1
FIGURE 1

Architecture of substrates of T1SS. The primary structure of a canonical substrate of a T1SS is shown as white cylinder with the N and C termini labeled by “N” and “C,” respectively. The secretion sequence (approximately 50 to 100 amino acids depending on the substrate) at the C terminus is in red, the GG repeats forming the classic RTX domain are in blue (six GG repeats as in the case of HlyA have been chosen as an example), and the functional, N-terminal domain is in brown. However, the number and types of architectures of this functional domain have increased in recent years. HlyA-like proteins contain only one domain with dedicated activity (pore-forming activity in the case of HlyA), while, for example, CyaA-like proteins contain two domains, which possess an adenylate cyclase (light brown) and a pore-forming (brown) activity in the case of CyaA. A third class are MARTX proteins (exemplified here by a MARTX protein from ). The effector domains (yellow and separated by black vertical lines) that are autocatalytically excised after secretion are flanked by an N-terminal RTX-like domain (marked as RTX domain*) and a C-terminal RTX domain. The C-terminal domain corresponds to the canonical sequence, while the conserved aspartate is missing in the N-terminal one. Another architecture is present in LapA-like adhesins (or bacterial transglutaminase-like cysteine proteinases) that contain multiple, different domains. In the case of LapA, two different colors indicate two different domains. However, the number of different domains is not restricted to two. Additionally, the double-alanine motif in the N termini of LapA-like RTX adhesins is not shown. Finally, SiiE-like adhesins contain multiple identical domains, such as the 53 copies of the BIg domain in the case of SiiE ( 6 , 71 ). The vertical blue line indicates that the GG repeats are integrated within the Ig-like domains and do not form a separate RTX domain. Please note that the drawing of the functional domains is not to scale.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.PSIB-0003-2018
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Image of FIGURE 2
FIGURE 2

Structure of GG repeats of alkaline protease (PDB entry 1KAP) from in its Ca-bound state, resulting in the classic β-roll motif. The five Ca ions are shown as blue spheres. For simplicity, only the first three GG repeats are shown in ball-and-stick representation. The carbon atoms of GG repeat one are in gray, the carbon atoms of the second GG repeat in green, and the ones of the third repeat in yellow. The interactions of repeat one with the bound Ca ion are indicated by gray dashed lines, and the interaction of the third repeat with the bound Ca ions is in yellow. As it is evident, one Ca ion is coordinated by repeat and repeat + 2. RTX domain of alkaline protease from in cartoon representation. The orientation is identical to that in panel A, and the gray and yellow dashed lines indicate the interactions.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.PSIB-0003-2018
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Image of FIGURE 3
FIGURE 3

Schematic summary of the classic T1SS-mediated substrate secretion and the recently discovered secretion mechanism for some RTX adhesins in which secretion stalls just before completion, creating a so-called two-step process with a pseudoperiplasmic intermediate . The ABC transporter and the MFP are shown in blue and green, respectively, and the OM protein is in maroon. The unfolded substrate is secreted with its C terminus first. At the cell surface, Ca ions (blue spheres) bind to the GG repeats and induce folding, which results in formation of the β-roll (indicated in cartoon representation). In the case of adhesins such as IBA or LapA, the N-terminal domain starts folding prior to or during secretion, which plugs the translocon (indicated by the light brown polygon) and tethers the entire substrate at the cell surface within the OM component of the translocon of the T1SS. The brown cubes and distorted ellipse represent folded domains of the substrate. This scheme clearly demonstrates that the classic T1SS disassembles only after the entire substrate is translocated, while in two-step T1SS disassembly earlier, e.g., when the N-terminal plug domain has not passed the OM. For further details, see the text. IM, inner membrane; NBD, nucleotide binding domain; TMD, transmembrane domain.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.PSIB-0003-2018
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