A Francisella tularensis L,D‐carboxypeptidase plays important roles in cell morphology, envelope integrity, and virulence
Autor: | Briana Zellner, William T. Gunning, Brenden G. Tully, Jason F. Huntley, Robert Booth, Dominique Mengin-Lecreulx |
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Přispěvatelé: | Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Enveloppes Bactériennes et Antibiotiques (ENVBAC), Département Microbiologie (Dpt Microbio), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
Rok vydání: | 2021 |
Předmět: |
Carboxypeptidases A
Neutrophils D-carboxypeptidase [SDV]Life Sciences [q-bio] Virulence peptidoglycan Biology Cell morphology Microbiology Bacterial cell structure Tularemia Mice 03 medical and health sciences chemistry.chemical_compound Cell Wall medicine Animals Amino Acid Sequence Francisella tularensis Molecular Biology Cells Cultured 030304 developmental biology Mice Inbred C3H 0303 health sciences 030306 microbiology Macrophages Intracellular parasite medicine.disease biology.organism_classification tularemia 3. Good health virulence Disease Models Animal chemistry Female Peptidoglycan Sequence Alignment Intracellular |
Zdroj: | Molecular Microbiology Molecular Microbiology, 2021, n/a (n/a), ⟨10.1111/mmi.14685⟩ |
ISSN: | 1365-2958 0950-382X |
DOI: | 10.1111/mmi.14685 |
Popis: | SummaryFrancisella tularensis is a Gram-negative, intracellular bacterium that causes the zoonotic disease tularemia. Intracellular pathogens, including F. tularensis, have evolved mechanisms to survive in the harsh environment of macrophages and neutrophils, where they are exposed to cell envelope-damaging molecules. The bacterial cell wall, primarily composed of peptidoglycan (PG), maintains cell morphology, structure, and membrane integrity. Intracellular Gram-negative bacteria protect themselves from macrophage and neutrophil killing by recycling and repairing damaged PG – a process that involves over 50 different PG synthesis and recycling enzymes. Here, we identified a PG recycling enzyme, L,D-carboxypeptidase A (LdcA), of F. tularensis that is responsible for converting PG tetrapeptide stems to tripeptide stems. Unlike E. coli LdcA and most other orthologs, F. tularensis LdcA does not localize to the cytoplasm and also exhibits L,D-endopeptidase activity, converting PG pentapeptide stems to tripeptide stems. Loss of F. tularensis LdcA led to altered cell morphology and membrane integrity, as well as attenuation in a mouse pulmonary infection model and in primary and immortalized macrophages. Finally, an F. tularensis ldcA mutant protected mice against virulent Type A F. tularensis SchuS4 pulmonary challenge. |
Databáze: | OpenAIRE |
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