Journal article
FTT0831c/FTL_0325 contributes to Francisella tularensis cell division, maintenance of cell shape, and structural integrity
Infection and immunity, Vol.82(7), pp.2935-2948
07/2014
Handle:
https://hdl.handle.net/2376/104927
PMCID: PMC4097634
PMID: 24778115
Abstract
The Francisella FTT0831c/FTL_0325 gene encodes amino acid motifs to suggest it is a lipoprotein and that it may interact with the bacterial cell wall as a member of the OmpA-like protein family. Previous studies have suggested that FTT0831c is surface exposed and required for virulence of Francisella tularensis by subverting the host innate immune response (M. Mahawar et al., J. Biol. Chem. 287:25216-25229, 2012). We also found that FTT0831c is required for murine pathogenesis and intramacrophage growth of Schu S4, but we propose a different model to account for the proinflammatory nature of the resultant mutants. First, inactivation of FTL_0325 from live vaccine strain (LVS) or FTT0831c from Schu S4 resulted in temperature-dependent defects in cell viability and morphology. Loss of FTT0831c was also associated with an unusual defect in lipopolysaccharide O-antigen synthesis, but loss of FTL_0325 was not. Full restoration of these properties was observed in complemented strains expressing FTT0831c in trans, but not in strains lacking the OmpA motif, suggesting that cell wall contact is required. Finally, growth of the LVS FTL_0325 mutant in Mueller-Hinton broth at 37°C resulted in the appearance of membrane blebs at the poles and midpoint, prior to the formation of enlarged round cells that showed evidence of compromised cellular membranes. Taken together, these data are more consistent with the known structural role of OmpA-like proteins in linking the OM to the cell wall and, as such, maintenance of structural integrity preventing altered surface exposure or release of Toll-like receptor 2 agonists during rapid growth of Francisella in vitro and in vivo.
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Details
- Title
- FTT0831c/FTL_0325 contributes to Francisella tularensis cell division, maintenance of cell shape, and structural integrity
- Creators
- Gregory T Robertson - Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USAElizabeth Di Russo Case - Laboratory of Intracellular Parasites, NIAID, National Institutes of Health Rocky Mountain Laboratories, Hamilton, Montana, USANicole Dobbs - Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USAChristine Ingle - Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USAMurat Balaban - Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USAJean Celli - Laboratory of Intracellular Parasites, NIAID, National Institutes of Health Rocky Mountain Laboratories, Hamilton, Montana, USAMichael V Norgard - Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA Michael.Norgard@UTSouthwestern.edu
- Publication Details
- Infection and immunity, Vol.82(7), pp.2935-2948
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- United States
- Grant note
- U54 AI057156 / NIAID NIH HHS
- Identifiers
- 99900546730001842
- Language
- English
- Resource Type
- Journal article