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Infection and Immunity, January 2007, p. 390-396, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01226-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

AcpA Is a Francisella Acid Phosphatase That Affects Intramacrophage Survival and Virulence{triangledown}

Nrusingh P. Mohapatra, Ashwin Balagopal, Shilpa Soni, Larry S. Schlesinger, and John S. Gunn*

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

Received 2 August 2006/ Returned for modification 20 September 2006/ Accepted 12 October 2006

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.


* Corresponding author. Mailing address: The Ohio State University, Tzagournis Medical Research Facility, 420 W. 12th Ave., Columbus, OH 43210-1214. Phone: (614) 292-6036. Fax: (614) 292-5495. E-mail: gunn.43{at}osu.edu.

{triangledown} Published ahead of print on 23 October 2006.

Editor: V. J. DiRita


Infection and Immunity, January 2007, p. 390-396, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01226-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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