A Francisella tularensis L,D-carboxypeptidase plays important roles in cell morphology, envelope integrity, and virulence.

作者: Briana Zellner , Dominique Mengin-Lecreulx , Brenden Tully , William T. Gunning , Robert Booth

DOI: 10.1101/817593

关键词: Cell morphologyBacterial cell structureMicrobiologyTularemiaIntracellularIntracellular parasiteVirulenceChemistryPeptidoglycanFrancisella tularensis

摘要: Francisella tularensis is a Gram-negative, intracellular bacterium that causes the zoonotic disease tularemia. Intracellular pathogens, including F. tularensis, have evolved mechanisms to survive in harsh environment of macrophages and neutrophils, where they are exposed cell membrane-damaging molecules. The bacterial wall, primarily composed peptidoglycan (PG), maintains morphology, structure, membrane integrity. Gram-negative bacteria protect themselves from macrophage neutrophil killing by recycling repairing damaged PG - process involves over 50 different synthesis enzymes. Here, we identified enzyme, L,D-carboxypeptidase A (LdcA), responsible for converting tetrapeptide stems tripeptide stems. Unlike E. coli LdcA most other orthologs, does not localize cytoplasm also exhibits L,D-endopeptidase activity, pentapeptide Loss led altered morphology integrity, as well attenuation mouse pulmonary infection model primary immortalized macrophages. Finally, an ldcA mutant protected mice against virulent Type SchuS4 challenge.

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