Acid phosphatases do not contribute to the pathogenesis of type A Francisella tularensis.
The intracellular pathogen Francisella tularensis is the causative agent of tularemia, a zoonosis that can affect humans with potentially lethal consequences. Essential to Francisella virulence is its ability to survive and proliferate within phagocytes through phagosomal escape and cytosolic replication. Francisella spp. encode a variety of acid phosphatases, whose roles in phagosomal escape and virulence have been documented yet remain controversial. Here we have examined in the highly virulent (type A) F. tularensis strain Schu S4 the pathogenic roles of three distinct acid phosphatases, AcpA, AcpB, and AcpC, that are most conserved between Francisella subspecies. Neither the deletion of acpA nor the combination of acpA, acpB, and acpC deletions affected the phagosomal escape or cytosolic growth of Schu S4 in murine and human macrophages, despite decreases in acid phosphatase activities by as much as 95%. Furthermore, none of these mutants were affected in their ability to cause lethality in mice upon intranasal inoculation. Hence, the acid phosphatases AcpA, AcpB, and AcpC do not contribute to intracellular pathogenesis and do not play a major role in the virulence of type A Francisella strains.
Child
Robert
R
Tularemia Pathogenesis Section, Laboratory of Intracellular Parasites, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, Hamilton, MT 59840, USA.
Wehrly
Tara D
TD
Rockx-Brouwer
Dedeke
D
Dorward
David W
DW
Celli
Jean
J
D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005604:Francisella tularensis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008807:Mice, Inbred BALB C; D014406:Tularemia / Q000382:microbiology*; D014774:Virulence
D000135:Acid Phosphatase