Structures of Type III Secretion System Needle Filaments

Habenstein, Birgit; Mammeri, Nadia El; Tolchard, James; Lamon, Gaëlle; Tawani, Arpita; Berbon, Mélanie; Loquet, Antoine

doi:10.1007/82_2019_192

Cited by 11 publications

(10 citation statements)

References 74 publications

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“…(B) The recognition of pathogen-related molecular patterns (PAMP) on the bacterial cells by receptors expressed on immune cells, triggers the release of cytokines and the recruitment of leukocytes that can initiate anti-tumor immune responses ( 29 – 31 ). (C) S. typhimurium uses a Type III secretion system which leads to the release of different factors into cancer cells, and the bacteria can also be internalized and undergo intra-cellular replication ( 32 , 33 ). (C.I) Cell stress responses are induced by invasive Salmonella cells mediated via danger-associated molecular patterns (DAMP) that also act as signals to the immune system.…”

Section: Salmonella Bacteria and Treatment Of Cancermentioning

confidence: 99%

“…However the antitumor effects of S. typhimurium in human (29)(30)(31). (C) S. typhimurium uses a Type III secretion system which leads to the release of different factors into cancer cells, and the bacteria can also be internalized and undergo intra-cellular replication (32,33). (C.I) Cell stress responses are induced by invasive Salmonella cells mediated via danger-associated molecular patterns (DAMP) that also act as signals to the immune system.…”

Section: Salmonella Bacteria As Delivery Systems For Anti-tumor Agentsmentioning

confidence: 99%

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Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

et al. 2021

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Over the years, conventional cancer treatments, such as chemotherapy with only a limited specificity for tumors, have undergone significant improvement. Moreover, newer therapies such as immunotherapy have undergone a revolution to stimulate the innate as well as adaptive immune responses against the tumor. However, it has been found that tumors can be selectively colonized by certain bacteria, where they can proliferate, and exert direct oncolytic effects as well as stimulating the immune system. Bacterial-mediated cancer therapy (BMCT) is now one example of a hot topic in the antitumor field. Salmonella typhimurium is a Gram-negative species that generally causes self-limiting gastroenteritis in humans. This species has been designed and engineered in order to be used in cancer-targeted therapeutics. S. typhimurium can be used in combination with other treatments such as chemotherapy or radiotherapy for synergistic modification of the tumor microenvironment. Considerable benefits have been shown by using engineered attenuated strains for the diagnosis and treatment of tumors. Some of these treatment approaches have received FDA approval for early-phase clinical trials. This review summarizes the use of Salmonella bacteria for cancer therapy, which could pave the way towards routine clinical application. The benefits of this therapy include an automatic self-targeting ability, and the possibility of genetic manipulation to produce newly engineered attenuated strains. Nevertheless, Salmonella-mediated anticancer therapy has not yet been clinically established, and requires more research before its use in cancer treatment.

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Section: Salmonella Bacteria and Treatment Of Cancermentioning

confidence: 99%

Section: Salmonella Bacteria As Delivery Systems For Anti-tumor Agentsmentioning

confidence: 99%

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

et al. 2021

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“…Structural studies revealed that several Sct proteins are involved in the assembly of the ring structures of the T3S system in the outer membrane (OM) and inner membrane (IM; Deng et al, 2017 ; Lara-Tejero and Galan, 2019 ). The OM ring of T3S systems is assembled by members of the SctC secretin family and is associated with an extracellular appendage which is referred to as T3S needle in animal- or pilus in plant-pathogenic bacteria and serves as a transport channel for secreted proteins to the host-pathogen interface ( Büttner, 2012 ; Deng et al, 2017 ; Habenstein et al, 2020 ). The translocation of effector proteins into eukaryotic target cells is mediated by the T3S translocon, which inserts as a homo- or heterooligomeric protein channel into the eukaryotic plasma membrane ( Mattei et al, 2011 ; Dey et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The Contribution of the Predicted Sorting Platform Component HrcQ to Type III Secretion in Xanthomonas campestris pv. vesicatoria Depends on an Internal Translation Start Site

et al. 2021

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Pathogenicity of the Gram-negative bacterium Xanthomonas campestris pv. vesicatoria depends on a type III secretion (T3S) system which translocates effector proteins into plant cells. T3S systems are conserved in plant- and animal-pathogenic bacteria and consist of at least nine structural core components, which are designated Sct (secretion and cellular translocation) in animal-pathogenic bacteria. Sct proteins are involved in the assembly of the membrane-spanning secretion apparatus which is associated with an extracellular needle structure and a cytoplasmic sorting platform. Components of the sorting platform include the ATPase SctN, its regulator SctL, and pod-like structures at the periphery of the sorting platform consisting of SctQ proteins. Members of the SctQ family form a complex with the C-terminal protein domain, SctQC, which is translated as separate protein and likely acts either as a structural component of the sorting platform or as a chaperone for SctQ. The sorting platform has been intensively studied in animal-pathogenic bacteria but has not yet been visualized in plant pathogens. We previously showed that the SctQ homolog HrcQ from X. campestris pv. vesicatoria assembles into complexes which associate with the T3S system and interact with components of the ATPase complex. Here, we report the presence of an internal alternative translation start site in hrcQ leading to the separate synthesis of the C-terminal protein region (HrcQC). The analysis of genomic hrcQ mutants showed that HrcQC is essential for pathogenicity and T3S. Increased expression levels of hrcQ or the T3S genes, however, compensated the lack of HrcQC. Interaction studies and protein analyses suggest that HrcQC forms a complex with HrcQ and promotes HrcQ stability. Furthermore, HrcQC colocalizes with HrcQ as was shown by fluorescence microscopy, suggesting that it is part of the predicted cytoplasmic sorting platform. In agreement with this finding, HrcQC interacts with the inner membrane ring protein HrcD and the SctK-like linker protein HrpB4 which contributes to the docking of the HrcQ complex to the membrane-spanning T3S apparatus. Taken together, our data suggest that HrcQC acts as a chaperone for HrcQ and as a structural component of the predicted sorting platform.

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“…Solid-state nuclear magnetic resonance spectroscopy (SSNMR) is a powerful technique to study insoluble, aggregated or non-crystalline biomaterials, ranging from biopolymers ((Kelly et al 2020), (Zhao et al 2020),(Goldberga et al 2018)), carbohydrates ((El Hariri El Nokab and van der Wel 2020)), RNA (Ahmed et al 2020) or membranes (Dufourc 2021),(Mallikarjunaiah et al 2019) to larger systems such as protein complexes(Demers et al 2018) large proteins (Vasa et al 2018)(Schütz 2021)), protein-ligand interaction ((Vasa et al 2019)(Elkins and Hong 2019),(Medeiros-Silva et al 2019)), misfolded proteins (König et al 2019), amyloid (Tycko 2016)fibrils ((Jaroniec 2019),(Loquet et al 2018)), helical filaments (Habenstein et al 2019), viruses (Lecoq et al 2020), (Gupta et al 2020), (Lu et al 2020)), membrane proteins (McDermott 2009)(Tang et al 2013)(Mandala et al 2018) or whole cells ((Narasimhan et al 2020)). In the two past decades, structural investigation of biomolecules at atomic resolution by SSNMR has made dramatic analytical improvements with the introduction of direct proton ( 1 H) detection(Ishii et al 2001)(Reif et al 2001)(Paulson et al 2003)(Zhou et al 2009) combined with the use of magic-angle spinning (MAS) probes operating at fast frequencies(Nishiyama 2016)(Böckmann et al 2015)(Cala-De Paepe et al 2017)(Sternberg et al 2018)(Xue et al 2018)(Ishii et al 2018)(Schledorn et al 2020), nowadays commercially available at MAS frequency of 60-110 kHz.…”

Section: Introductionmentioning

confidence: 99%

Protein resonance assignment by solid-state NMR based on ¹H-detected ¹³C-based double-quantum spectroscopy at fast MAS

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Habenstein

et al. 2021

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Solid-state NMR spectroscopy is a powerful technique to study insoluble and non-crystalline proteins and protein complexes at atomic resolution. The development of proton (1H) detection at fast magic-angle spinning (MAS) has considerably increased the analytical capabilities of the technique, enabling the acquisition of 1H-detected fingerprint experiments in few hours. Here an approach based on double-quantum (DQ) 13C spectroscopy, detected on 1H, is introduced at fast MAS (70 kHz) to perform the sequential assignment of insoluble proteins of small size, without any specific deuteration requirement. By combining two three-dimensional 1H detected experiments correlating a 13C DQ dimension respectively to its intra-residue and sequential 15N-1H pairs, a sequential walk through DQ (CA+CO) resonance is obtained. Our approach takes advantage of fast MAS to achieve an efficient sensitivity and the addition of a DQ dimension provides spectral features useful for the resonance assignment process.

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Structures of Type III Secretion System Needle Filaments

Cited by 11 publications

References 74 publications

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

The Contribution of the Predicted Sorting Platform Component HrcQ to Type III Secretion in Xanthomonas campestris pv. vesicatoria Depends on an Internal Translation Start Site

Protein resonance assignment by solid-state NMR based on ¹H-detected ¹³C-based double-quantum spectroscopy at fast MAS

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Structures of Type III Secretion System Needle Filaments

Cited by 11 publications

References 74 publications

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches

The Contribution of the Predicted Sorting Platform Component HrcQ to Type III Secretion in Xanthomonas campestris pv. vesicatoria Depends on an Internal Translation Start Site

Protein resonance assignment by solid-state NMR based on 1H-detected 13C-based double-quantum spectroscopy at fast MAS

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Protein resonance assignment by solid-state NMR based on ¹H-detected ¹³C-based double-quantum spectroscopy at fast MAS