A Francisella novicida pdpA mutant exhibits limited intracellular replication and remains associated with the lysosomal marker LAMP-1
- 1 May 2009
- journal article
- Published by Microbiology Society in Microbiology
- Vol. 155 (5), 1498-1504
- https://doi.org/10.1099/mic.0.025445-0
Abstract
Several genes contained in the Francisella pathogenicity island (FPI) encode proteins needed for intracellular growth and virulence of Francisella tularensis. The pdpA gene is the first cistron in the larger of the two operons found in the FPI. In this work we studied the intracellular growth phenotype of a Francisella novicida mutant in the pdpA gene. The ΔpdpA strain was capable of a small amount of intracellular replication but, unlike wild-type F. novicida, remained associated with the lysosomal marker LAMP-1, suggesting that PdpA is necessary for progression from the early phagosome phase of infection. Strains with in cis complementation of the ΔpdpA lesion showed a restoration of intracellular growth to wild-type levels. Infection of macrophages with the ΔpdpA mutant generated a host-cell mRNA profile distinct from that generated by infection with wild-type F. novicida. The transcriptional response of the host macrophage indicates that PdpA functions directly or indirectly to suppress macrophage ability to signal via growth factors, cytokines and adhesion ligands.Keywords
This publication has 29 references indexed in Scilit:
- Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicidaMicrobiology, 2009
- The Early Phagosomal Stage of Francisella tularensis Determines Optimal Phagosomal Escape and Francisella Pathogenicity Island Protein ExpressionInfection and Immunity, 2008
- Combined Deletion of Four Francisella novicida Acid Phosphatases Attenuates Virulence and Macrophage Vacuolar EscapeInfection and Immunity, 2008
- MglA and Igl Proteins Contribute to the Modulation ofFrancisella tularensisLive Vaccine Strain-Containing Phagosomes in Murine MacrophagesInfection and Immunity, 2008
- TheFrancisellaPathogenicity Island Protein PdpD Is Required for Full Virulence and Associates with Homologues of the Type VI Secretion SystemJournal of Bacteriology, 2008
- Generation and Characterization of an Attenuated Mutant in a Response Regulator Gene ofFrancisella tularensisLive Vaccine Strain (LVS)DNA and Cell Biology, 2008
- Acquisition of the Vacuolar ATPase Proton Pump and Phagosome Acidification Are Essential for Escape of Francisella tularensis into the Macrophage CytosolInfection and Immunity, 2008
- In vivo negative selection screen identifies genes required for Francisella virulenceProceedings of the National Academy of Sciences, 2007
- Francisella tularensis Replicates within Alveolar Type II Epithelial Cells In Vitro and In Vivo following InhalationInfection and Immunity, 2007
- AcpA Is aFrancisellaAcid Phosphatase That Affects Intramacrophage Survival and VirulenceInfection and Immunity, 2007