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Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity

D-alanyl-D-alanine carboxypeptidase, product of dacD gene in Francisella, belongs to penicillin binding proteins (PBPs) and is involved in remodeling of newly synthetized peptidoglycan. In E. coli, PBPs are synthetized in various growth phases and they are able to substitute each other to a certain...

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Autores principales: Spidlova, Petra, Stojkova, Pavla, Dankova, Vera, Senitkova, Iva, Santic, Marina, Pinkas, Dominik, Philimonenko, Vlada, Stulik, Jiri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903032/
https://www.ncbi.nlm.nih.gov/pubmed/29692981
http://dx.doi.org/10.3389/fcimb.2018.00111
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author Spidlova, Petra
Stojkova, Pavla
Dankova, Vera
Senitkova, Iva
Santic, Marina
Pinkas, Dominik
Philimonenko, Vlada
Stulik, Jiri
author_facet Spidlova, Petra
Stojkova, Pavla
Dankova, Vera
Senitkova, Iva
Santic, Marina
Pinkas, Dominik
Philimonenko, Vlada
Stulik, Jiri
author_sort Spidlova, Petra
collection PubMed
description D-alanyl-D-alanine carboxypeptidase, product of dacD gene in Francisella, belongs to penicillin binding proteins (PBPs) and is involved in remodeling of newly synthetized peptidoglycan. In E. coli, PBPs are synthetized in various growth phases and they are able to substitute each other to a certain extent. The DacD protein was found to be accumulated in fraction enriched in membrane proteins from severely attenuated dsbA deletion mutant strain. It has been presumed that the DsbA is not a virulence factor by itself but that its substrates, whose correct folding and topology are dependent on the DsbA oxidoreductase and/or isomerase activities, are the primary virulence factors. Here we demonstrate that Francisella DacD is required for intracellular replication and virulence in mice. The dacD insertion mutant strain showed higher sensitivity to acidic pH, high temperature and high osmolarity when compared to the wild-type. Eventually, transmission electron microscopy revealed differences in mutant bacteria in both the size and defects in outer membrane underlying its SDS and serum sensitivity. Taken together these results suggest DacD plays an important role in Francisella pathogenicity.
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spelling pubmed-59030322018-04-24 Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity Spidlova, Petra Stojkova, Pavla Dankova, Vera Senitkova, Iva Santic, Marina Pinkas, Dominik Philimonenko, Vlada Stulik, Jiri Front Cell Infect Microbiol Microbiology D-alanyl-D-alanine carboxypeptidase, product of dacD gene in Francisella, belongs to penicillin binding proteins (PBPs) and is involved in remodeling of newly synthetized peptidoglycan. In E. coli, PBPs are synthetized in various growth phases and they are able to substitute each other to a certain extent. The DacD protein was found to be accumulated in fraction enriched in membrane proteins from severely attenuated dsbA deletion mutant strain. It has been presumed that the DsbA is not a virulence factor by itself but that its substrates, whose correct folding and topology are dependent on the DsbA oxidoreductase and/or isomerase activities, are the primary virulence factors. Here we demonstrate that Francisella DacD is required for intracellular replication and virulence in mice. The dacD insertion mutant strain showed higher sensitivity to acidic pH, high temperature and high osmolarity when compared to the wild-type. Eventually, transmission electron microscopy revealed differences in mutant bacteria in both the size and defects in outer membrane underlying its SDS and serum sensitivity. Taken together these results suggest DacD plays an important role in Francisella pathogenicity. Frontiers Media S.A. 2018-04-10 /pmc/articles/PMC5903032/ /pubmed/29692981 http://dx.doi.org/10.3389/fcimb.2018.00111 Text en Copyright © 2018 Spidlova, Stojkova, Dankova, Senitkova, Santic, Pinkas, Philimonenko and Stulik. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Spidlova, Petra
Stojkova, Pavla
Dankova, Vera
Senitkova, Iva
Santic, Marina
Pinkas, Dominik
Philimonenko, Vlada
Stulik, Jiri
Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity
title Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity
title_full Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity
title_fullStr Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity
title_full_unstemmed Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity
title_short Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity
title_sort francisella tularensis d-ala d-ala carboxypeptidase dacd is involved in intracellular replication and it is necessary for bacterial cell wall integrity
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903032/
https://www.ncbi.nlm.nih.gov/pubmed/29692981
http://dx.doi.org/10.3389/fcimb.2018.00111
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