Rationale redesign of type III secretion systems: toward the development of non-pathogenic E. coli for in vivo delivery of therapeutic payloads

González-Prieto, Coral; Lesser, Cammie F.

doi:10.1016/j.mib.2017.10.011

Cited by 18 publications

(12 citation statements)

References 47 publications

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“…Advances in our understanding of T3SS will foster the exploitation of this intricate system for therapeutic (Bai et al. 2018 ; González-Prieto and Lesser 2018 ) and biotechnological (Widmaier et al. 2009 ; Singer et al.…”

Section: Discussionmentioning

confidence: 99%

Bacterial type III secretion systems: a complex device for the delivery of bacterial effector proteins into eukaryotic host cells

Wagner

Grin

Malmsheimer

et al. 2018

FEMS Microbiology Letters

155

134

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Virulence-associated type III secretion systems (T3SS) serve the injection of bacterial effector proteins into eukaryotic host cells. They are able to secrete a great diversity of substrate proteins in order to modulate host cell function, and have evolved to sense host cell contact and to inject their substrates through a translocon pore in the host cell membrane. T3SS substrates contain an N-terminal signal sequence and often a chaperone-binding domain for cognate T3SS chaperones. These signals guide the substrates to the machine where substrates are unfolded and handed over to the secretion channel formed by the transmembrane domains of the export apparatus components and by the needle filament. Secretion itself is driven by the proton motive force across the bacterial inner membrane. The needle filament measures 20–150 nm in length and is crowned by a needle tip that mediates host-cell sensing. Secretion through T3SS is a highly regulated process with early, intermediate and late substrates. A strict secretion hierarchy is required to build an injectisome capable of reaching, sensing and penetrating the host cell membrane, before host cell-acting effector proteins are deployed. Here, we review the recent progress on elucidating the assembly, structure and function of T3SS injectisomes.

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Section: Discussionmentioning

confidence: 99%

Bacterial type III secretion systems: a complex device for the delivery of bacterial effector proteins into eukaryotic host cells

Wagner

Grin

Malmsheimer

et al. 2018

FEMS Microbiology Letters

155

134

View full text Add to dashboard Cite

show abstract

“…Finally, VgpA’s capacity to stimulate intestinal cell proliferation could potentially be harnessed for the treatment of diseases, such as inflammatory bowel disease, associated with intestinal epithelial injury. It may be possible to deliver VgpA to damaged tissue by a V. parahaemolyticus mutant that can robustly colonize the intestine without causing disease (Zhou et al , 2013) or via a probiotic strain like E. coli Nissle engineered to express a heterologous T3SS (Gonzalez‐Prieto & Lesser, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Source data are available online for this figure. without causing disease (Zhou et al, 2013) or via a probiotic strain like E. coli Nissle engineered to express a heterologous T3SS (Gonzalez-Prieto & Lesser, 2018).…”

Section: Discussionmentioning

confidence: 99%

Nucleolar c‐Myc recruitment by a Vibrio T3SS effector promotes host cell proliferation and bacterial virulence

Zhang

et al. 2020

The EMBO Journal

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Pathogen type 3 secretion systems (T3SS) manipulate host cell pathways by directly delivering effector proteins into host cells. In Vibrio parahaemolyticus, the leading cause of bacterial seafood‐borne diarrheal disease, we showed that a T3SS effector, VgpA, localizes to the host cell nucleolus where it binds Epstein–Barr virus nuclear antigen 1‐binding protein 2 (EBP2). An amino acid substitution in VgpA (VgpAL10A) did not alter its translocation to the nucleus but abolished the effector’s capacity to interact with EBP2. VgpA‐EBP2 interaction led to the re‐localization of c‐Myc to the nucleolus and increased cellular rRNA expression and proliferation of cultured cells. The VgpA‐EBP2 interaction elevated EBP2’s affinity for c‐Myc and prolonged the oncoprotein’s half‐life. Studies in infant rabbits demonstrated that VgpA is translocated into intestinal epithelial cells, where it interacts with EBP2 and leads to nucleolar re‐localization of c‐Myc. Moreover, the in vivo VgpA‐EBP2 interaction during infection led to proliferation of intestinal cells and heightened V. parahaemolyticus’ colonization and virulence. These observations suggest that direct effector stimulation of a c‐Myc controlled host cell growth program can contribute to pathogenesis.

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“…The effectiveness of probiotics is dependent on the successful establishment of probiotics in the gut. The secretion system (Type III or VI) of P. fungorum is highly responsible for survival, adhesion, and adaptation [ 38 ]. The type III secretion system is a nanomachine that delivers effector proteins into the host cell to mediate pathogenesis [ 38 ], and type VI is a toxin delivery system which antagonizes competitors [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary Administration of Novel Multistrain Probiotics from Healthy Grouper Intestines Promotes the Intestinal Immune Response against NNV Infection

Joe

Sung

et al. 2021

Life

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Epinephelus lanceolatus (giant grouper) is a high-value cultured species in the Asia-Pacific region. However, nervous necrosis virus (NNV) is an infectious viral disease that affects over 120 species of marine cultured species and causes high mortality, ranging from 90–100% in the grouper industry. Probiotics isolated from the intestines of healthy individuals have provided insight into novel approaches involved in the defense against viral pathogens. In this study, we isolated three strains of bacteria as candidate probiotics from healthy grouper intestines and a 28-day feeding trial was performed. At day 21, the nervous necrosis virus (NNV) challenge test was conducted for 7 days to evaluate the antiviral effect of candidate probiotics. The results showed that candidate probiotics could improve growth conditions, such as weight gain (WG) and specific growth rate (SGR), and increase the utilization of feed. Furthermore, the candidate probiotic mixture had the ability to protect against NNV, which could decrease the mortality rate by 100% in giant grouper after NNV challenge. Subsequently, we analyzed the mechanism of the candidate probiotic mixture’s defense against NNV. A volcano plot revealed 203 (control vs. NNV), 126 (NNV vs. probiotics–NNV), and 5 (control vs. probiotics–NNV) differentially expressed transcripts in intestinal tissue. Moreover, principal components analysis (PCA) and cluster analysis heatmap showed large differences among the three groups. Functional pathway analysis showed that the candidate probiotic mixture could induce the innate and adaptive immunity of the host to defend against virus pathogens. Therefore, we hope that potential candidate probiotics could be successfully applied to the industry to achieve sustainable aquaculture.

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Rationale redesign of type III secretion systems: toward the development of non-pathogenic E. coli for in vivo delivery of therapeutic payloads

Cited by 18 publications

References 47 publications

Bacterial type III secretion systems: a complex device for the delivery of bacterial effector proteins into eukaryotic host cells

Bacterial type III secretion systems: a complex device for the delivery of bacterial effector proteins into eukaryotic host cells

Nucleolar c‐Myc recruitment by a Vibrio T3SS effector promotes host cell proliferation and bacterial virulence

Dietary Administration of Novel Multistrain Probiotics from Healthy Grouper Intestines Promotes the Intestinal Immune Response against NNV Infection

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