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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fcimb.2018.00111/full |
| _version_ | 1811327166419304448 |
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| author | Petra Spidlova Pavla Stojkova Vera Dankova Iva Senitkova Marina Santic Dominik Pinkas Vlada Philimonenko Vlada Philimonenko Jiri Stulik |
| author_facet | Petra Spidlova Pavla Stojkova Vera Dankova Iva Senitkova Marina Santic Dominik Pinkas Vlada Philimonenko Vlada Philimonenko Jiri Stulik |
| author_sort | Petra Spidlova |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T15:01:58Z |
| format | Article |
| id | doaj.art-19f123f88b654505877f6947bd9ce4d1 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-13T15:01:58Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-19f123f88b654505877f6947bd9ce4d12022-12-22T02:42:15ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-04-01810.3389/fcimb.2018.00111334445Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall IntegrityPetra Spidlova0Pavla Stojkova1Vera Dankova2Iva Senitkova3Marina Santic4Dominik Pinkas5Vlada Philimonenko6Vlada Philimonenko7Jiri Stulik8Department of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, CzechiaDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, CzechiaDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, CzechiaDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, CzechiaDepartment of Microbiology and Parasitology, Medical Faculty, University of Rijeka, Rijeka, CroatiaMicroscopy Center, Institute of Molecular Genetics ASCR v.v.i., Electron Microscopy Core Facility, Prague, CzechiaMicroscopy Center, Institute of Molecular Genetics ASCR v.v.i., Electron Microscopy Core Facility, Prague, CzechiaDepartment of Biology of the Cell Nucleus, Institute of Molecular Genetics ASCR v.v.i., Prague, CzechiaDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, CzechiaD-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.http://journal.frontiersin.org/article/10.3389/fcimb.2018.00111/fullFrancisellaDacDvirulencephagosomal escapecarboxypeptidasepenicillin binding proteins |
| spellingShingle | Petra Spidlova Pavla Stojkova Vera Dankova Iva Senitkova Marina Santic Dominik Pinkas Vlada Philimonenko Vlada Philimonenko Jiri Stulik Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity Frontiers in Cellular and Infection Microbiology Francisella DacD virulence phagosomal escape carboxypeptidase penicillin binding proteins |
| 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 | Francisella DacD virulence phagosomal escape carboxypeptidase penicillin binding proteins |
| url | http://journal.frontiersin.org/article/10.3389/fcimb.2018.00111/full |
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