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Infect. Immun. doi:10.1128/IAI.01226-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

AcpA: A Francisella Acid Phosphatase Affecting Intramacrophage Survival and Virulence

The 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, OH 43210 USA

^* To whom correspondence should be addressed. Email: gunn.43{at}osu.edu.

	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 versus 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 hrs 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 hrs post-infection. Thus, AcpA affects intracellular trafficking and the fate of Francisella within host macrophages.

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