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  1. Article ; Online: Recruitment of heterologous substrates by bacterial secretion systems for transkingdom translocation.

    Guzmán-Herrador, Dolores L / Fernández-Gómez, Andrea / Llosa, Matxalen

    Frontiers in cellular and infection microbiology

    2023  Volume 13, Page(s) 1146000

    Abstract: Bacterial secretion systems mediate the selective exchange of macromolecules between bacteria and their environment, playing a pivotal role in processes such as horizontal gene transfer or virulence. Among the different families of secretion systems, ... ...

    Abstract Bacterial secretion systems mediate the selective exchange of macromolecules between bacteria and their environment, playing a pivotal role in processes such as horizontal gene transfer or virulence. Among the different families of secretion systems, Type III, IV and VI (T3SS, T4SS and T6SS) share the ability to inject their substrates into human cells, opening up the possibility of using them as customized injectors. For this to happen, it is necessary to understand how substrates are recruited and to be able to engineer secretion signals, so that the transmembrane machineries can recognize and translocate the desired substrates in place of their own. Other factors, such as recruiting proteins, chaperones, and the degree of unfolding required to cross through the secretion channel, may also affect transport. Advances in the knowledge of the secretion mechanism have allowed heterologous substrate engineering to accomplish translocation by T3SS, and to a lesser extent, T4SS and T6SS into human cells. In the case of T4SS, transport of nucleoprotein complexes adds a bonus to its biotechnological potential. Here, we review the current knowledge on substrate recognition by these secretion systems, the many examples of heterologous substrate translocation by engineering of secretion signals, and the current and future biotechnological and biomedical applications derived from this approach.
    MeSH term(s) Humans ; Bacterial Secretion Systems/genetics ; Bacteria/metabolism ; Virulence ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Type IV Secretion Systems/metabolism
    Chemical Substances Bacterial Secretion Systems ; Bacterial Proteins ; Type IV Secretion Systems
    Language English
    Publishing date 2023-03-06
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2023.1146000
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Conjugative DNA Transfer From

    Samperio, Sara / Guzmán-Herrador, Dolores L / May-Cuz, Rigoberto / Martín, Maria Cruz / Álvarez, Miguel A / Llosa, Matxalen

    Frontiers in microbiology

    2021  Volume 12, Page(s) 606629

    Abstract: Lactic acid bacteria (LAB) belonging to the genus classically known ... ...

    Abstract Lactic acid bacteria (LAB) belonging to the genus classically known as
    Language English
    Publishing date 2021-02-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.606629
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens.

    Guzmán-Herrador, Dolores L / Steiner, Samuel / Alperi, Anabel / González-Prieto, Coral / Roy, Craig R / Llosa, Matxalen

    Frontiers in microbiology

    2017  Volume 8, Page(s) 1503

    Abstract: We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human ... ...

    Abstract We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen
    Language English
    Publishing date 2017-08-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2017.01503
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Substrate translocation involves specific lysine residues of the central channel of the conjugative coupling protein TrwB.

    Larrea, Delfina / de Paz, Héctor D / Matilla, Inmaculada / Guzmán-Herrador, Dolores L / Lasso, Gorka / de la Cruz, Fernando / Cabezón, Elena / Llosa, Matxalen

    Molecular genetics and genomics : MGG

    2017  

    Abstract: Conjugative transfer of plasmid R388 requires the coupling protein TrwB for protein and DNA transport, but their molecular role in transport has not been deciphered. We investigated the role of residues protruding into the central channel of the TrwB ... ...

    Abstract Conjugative transfer of plasmid R388 requires the coupling protein TrwB for protein and DNA transport, but their molecular role in transport has not been deciphered. We investigated the role of residues protruding into the central channel of the TrwB hexamer by a mutational analysis. Mutations affecting lysine residues K275, K398, and K421, and residue S441, all facing the internal channel, affected transport of both DNA and the relaxase protein in vivo. The ATPase activity of the purified soluble variants was affected significantly in the presence of accessory protein TrwA or DNA, correlating with their behaviour in vivo. Alteration of residues located at the cytoplasmic or the inner membrane interface resulted in lower activity in vivo and in vitro, while variants affecting residues in the central region of the channel showed increased DNA and protein transfer efficiency and higher ATPase activity, especially in the absence of TrwA. In fact, these variants could catalyze DNA transfer in the absence of TrwA under conditions in which the wild-type system was transfer deficient. Our results suggest that protein and DNA molecules have the same molecular requirements for translocation by Type IV secretion systems, with residues at both ends of the TrwB channel controlling the opening-closing mechanism, while residues embedded in the channel would set the pace for substrate translocation (both protein and DNA) in concert with TrwA.
    Language English
    Publishing date 2017-06-08
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2044817-X
    ISSN 1617-4623 ; 1617-4615
    ISSN (online) 1617-4623
    ISSN 1617-4615
    DOI 10.1007/s00438-017-1331-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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