title: Type A Francisella tularensis acid phosphatases contribute to pathogenesis.
abstract: Different Francisella spp. produce five or six predicted acid phosphatases (AcpA, AcpB, AcpC, AcpD, HapA and HapB). The genes encoding the histidine acid phosphatases (hapA, hapB) and acpD of F. tularensis subsp. Schu S4 strain are truncated or disrupted. However, deletion of HapA (FTT1064) in F. tularensis Schu S4 resulted in a 33% reduction in acid phosphatase activity and loss of the four functional acid phosphatases in F. tularensis Schu S4 (ΔABCH) resulted in a>99% reduction in acid phosphatase activity compared to the wild type strain. All single, double and triple mutants tested, demonstrated a moderate decrease in mouse virulence and survival and growth within human and murine phagocytes, whereas the ΔABCH mutant showed >3.5-fold decrease in intramacrophage survival and 100% attenuation of virulence in mouse. While the Schu S4 ΔABCH strain was attenuated in the mouse model, it showed only limited protection against wild type challenge. F. tularensis Schu S4 failed to stimulate reactive oxygen species production in phagocytes, whereas infection by the ΔABCH strain stimulated 5- and 56-fold increase in reactive oxygen species production in neutrophils and human monocyte-derived macrophages, respectively. The ΔABCH mutant but not the wild type strain strongly co-localized with p47 (phox) and replicated in macrophages isolated from p47 (phox) knockout mice. Thus, F. tularensis Schu S4 acid phosphatases, including the truncated HapA, play a major role in intramacrophage survival and virulence of this human pathogen.
authors: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, United States of America.
authors: Nrusingh P
authors: NP
authors: Mohapatra
authors: Shilpa
authors: S
authors: Soni
authors: Murugesan V S
authors: MV
authors: Rajaram
authors: Kristi L
authors: KL
authors: Strandberg
authors: John S
authors: JS
authors: Gunn
mesh_terms: D000135:Acid Phosphatase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D005604:Francisella tularensis / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000382:microbiology; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000382:microbiology; D010588:Phagosomes / Q000382:microbiology; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D000135:Acid Phosphatase