title: AcpA is a Francisella acid phosphatase that affects intramacrophage survival and virulence.
abstract: AcpA of Francisella spp. is a respiratory-burst-inhibiting acid phosphatase that also exhibits phospholipase C activity. To better understand the molecular basis of AcpA in virulence, a deletion of acpA was constructed in Francisella novicida. The phosphatase and lipase activities were reduced 10-fold and 8-fold, respectively, in the acpA mutant compared to the wild type and were found mostly associated with the outer membrane. The acpA mutant was more susceptible to intracellular killing than the wild-type strain in the THP-1 human macrophage-like cell line. In addition, mice infected with the acpA mutant survived longer than the wild-type strain and were less fit than the wild-type strain in competition infection assays. Transmission electron microscopy showed that the acpA mutant was delayed in escape from macrophage phagosomes, as more than 75% of acpA mutant bacteria could still be found inside phagosomes after 12 h of infection in THP-1 cells and human monocyte-derived macrophages, whereas most of the wild-type bacteria had escaped from the phagosome by 6 h postinfection. Thus, AcpA affects intracellular trafficking and the fate of Francisella within host macrophages.
authors.affiliation: Center for Microbial Interface Biology, Department of Molecular Virology, Immunology, and Medical Genetics, and Department of Internal Medicine, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Nrusingh P
authors.initials: NP
authors.lastname: Mohapatra
authors.forename: Ashwin
authors.initials: A
authors.lastname: Balagopal
authors.forename: Shilpa
authors.initials: S
authors.lastname: Soni
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
authors.forename: John S
authors.initials: JS
authors.lastname: Gunn
mesh_terms: D000135:Acid Phosphatase / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival; D005260:Female; D005603:Francisella / Q000201:enzymology / Q000472:pathogenicity*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D016133:Polymerase Chain Reaction; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D000135:Acid Phosphatase