scholarly journals The Photorhabdus asymbiotica virulence cassettes deliver protein effectors directly into target eukaryotic cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Isabella Vlisidou ◽  
Alexia Hapeshi ◽  
Joseph RJ Healey ◽  
Katie Smart ◽  
Guowei Yang ◽  
...  

Photorhabdus is a highly effective insect pathogen and symbiont of insecticidal nematodes. To exert its potent insecticidal effects, it elaborates a myriad of toxins and small molecule effectors. Among these, the Photorhabdus Virulence Cassettes (PVCs) represent an elegant self-contained delivery mechanism for diverse protein toxins. Importantly, these self-contained nanosyringes overcome host cell membrane barriers, and act independently, at a distance from the bacteria itself. In this study, we demonstrate that Pnf, a PVC needle complex associated toxin, is a Rho-GTPase, which acts via deamidation and transglutamination to disrupt the cytoskeleton. TEM and Western blots have shown a physical association between Pnf and its cognate PVC delivery mechanism. We demonstrate that for Pnf to exert its effect, translocation across the cell membrane is absolutely essential.

2019 ◽  
Author(s):  
Isabella Vlisidou ◽  
Alexia Hapeshi ◽  
Joseph R. J. Healey ◽  
Katie Smart ◽  
Guowei Yang ◽  
...  

AbstractPhotorhabdusis a highly effective insect pathogen and symbiont of insecticidal nematodes. To exert its potent insecticidal effects, it elaborates a myriad of toxins and small molecule effectors. Among these, thePhotorhabdusVirulence Cassettes (PVCs) represent an elegant self-contained delivery mechanism for diverse protein toxins. Importantly, these self-contained nanosyringes overcome host cell membrane barriers, and act independently, at a distance from the bacteria itself. In this study, we demonstrate that Pnf, a PVC needle complex associated toxin, is a Rho-GTPase, which acts via deamidation and transglutamination to disrupt the cytoskeleton. TEM and Western blots have shown a physical association between Pnf and its cognate PVC delivery mechanism. We demonstrate that for Pnf to exert its effect, translocation across the cell membrane is absolutely essential.SIGNIFICANCE STATEMENTHere we provide an up to date analysis of the nano-scale syringe-like molecular devices thatPhotorhabdususe to manipulate invertebrate hosts, the PVC system. They are related to theSerratiaAnti-Feeding Prophage and the Psuedoalteromonas MAC system. All these systems are in turn more distantly related to the well characterized Type VI secretion system currently receiving a great deal of attention. We demonstrate for the first time that the PVC nanosyringes are physically “loaded” with an effector protein payload before being freely released. The PVCs therefore represent bacterial molecular machines that are used as “long-range” protein delivery systems. This widespread class of toxin delivery system will likely prove of great significance in understanding many diverse bacteria/host interactions in future.


Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 238
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Jacek Z. Kubiak ◽  
Rafik M. Ghobrial

Human placenta formation relies on the interaction between fused trophoblast cells of the embryo with uterine endometrium. The fusion between trophoblast cells, first into cytotrophoblast and then into syncytiotrophoblast, is facilitated by the fusogenic protein syncytin. Syncytin derives from an envelope glycoprotein (ENV) of retroviral origin. In exogenous retroviruses, the envelope glycoproteins coded by env genes allow fusion of the viral envelope with the host cell membrane and entry of the virus into a host cell. During mammalian evolution, the env genes have been repeatedly, and independently, captured by various mammalian species to facilitate the formation of the placenta. Such a shift in the function of a gene, or a trait, for a different purpose during evolution is called an exaptation (co-option). We discuss the structure and origin of the placenta, the fusogenic and non-fusogenic functions of syncytin, and the mechanism of cell fusion. We also comment on an alleged danger of the COVID-19 vaccine based on the presupposed similarity between syncytin and the SARS-CoV-2 spike protein.


2021 ◽  
Author(s):  
Lucio Ayres Caldas ◽  
Fabiana Avila Carneiro ◽  
Fabio Luis Monteiro ◽  
Ingrid Augusto ◽  
Luiza Mendonça Higa ◽  
...  

1998 ◽  
Vol 23 (3) ◽  
pp. 159-168 ◽  
Author(s):  
Cristina Pacheco-Soares ◽  
Wanderley De Souza

2017 ◽  
Author(s):  
Rahul Chaudhari ◽  
Vishakha Dey ◽  
Aishwarya Narayan ◽  
Shobhona Sharma ◽  
Swati Patankar

The secretory pathway in Plasmodium falciparum has evolved to transport proteins to the host cell membrane and to an endosymbiotic organelle, the apicoplast. The latter can occur via the ER or the ER-Golgi route. Here, we study these three routes using proteins Erythrocyte Membrane Protein-1 (PfEMP1), Acyl Carrier Protein (ACP) and glutathione peroxidase-like thioredoxin peroxidase (PfTPxGl) and inhibitors of vesicular transport. As expected, the G protein dependent vesicular fusion inhibitor AlF4- and microtubule destabilizing drug vinblastine block the trafficking of PfEMP-1, a protein secreted to the host cell membrane. However, while both PfTPxGl and ACP are targeted to the apicoplast, only ACP trafficking remains unaffected by these treatments. This implies that G-protein dependent vesicles do not play a role in classical apicoplast protein targeting. Unlike the soluble protein ACP, we show that PfTPxGl is localized to the outermost membrane of the apicoplast. Thus, the parasite apicoplast acquires proteins via two different pathways: first, the vesicular trafficking pathway appears to handle not only secretory proteins, but an apicoplast membrane protein, PfTPxGl. Second, trafficking of apicoplast luminal proteins appear to be independent of G-protein coupled vesicles.


2017 ◽  
Author(s):  
Rahul Chaudhari ◽  
Vishakha Dey ◽  
Aishwarya Narayan ◽  
Shobhona Sharma ◽  
Swati Patankar

The secretory pathway in Plasmodium falciparum has evolved to transport proteins to the host cell membrane and to an endosymbiotic organelle, the apicoplast. The latter can occur via the ER or the ER-Golgi route. Here, we study these three routes using proteins Erythrocyte Membrane Protein-1 (PfEMP1), Acyl Carrier Protein (ACP) and glutathione peroxidase-like thioredoxin peroxidase (PfTPxGl) and inhibitors of vesicular transport. As expected, the G protein dependent vesicular fusion inhibitor AlF4- and microtubule destabilizing drug vinblastine block the trafficking of PfEMP-1, a protein secreted to the host cell membrane. However, while both PfTPxGl and ACP are targeted to the apicoplast, only ACP trafficking remains unaffected by these treatments. This implies that G-protein dependent vesicles do not play a role in classical apicoplast protein targeting. Unlike the soluble protein ACP, we show that PfTPxGl is localized to the outermost membrane of the apicoplast. Thus, the parasite apicoplast acquires proteins via two different pathways: first, the vesicular trafficking pathway appears to handle not only secretory proteins, but an apicoplast membrane protein, PfTPxGl. Second, trafficking of apicoplast luminal proteins appear to be independent of G-protein coupled vesicles.


MEMBRANE ◽  
2005 ◽  
Vol 30 (2) ◽  
pp. 68-72
Author(s):  
Ayato Takada ◽  
Takeshi Noda ◽  
Yoshihiro Kawaoka

2020 ◽  
Vol 6 (9) ◽  
pp. 2386-2399 ◽  
Author(s):  
Manjari Mishra ◽  
Ruchika Dadhich ◽  
Pankaj Mogha ◽  
Shobhna Kapoor

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