Acid phosphatase activity in Coxiella burnetii: a possible virulence factor.
High-speed supernatant fluids derived from sonicated Coxiella burnetii contained considerable acid phosphatase activity when assayed by using 4-methylumbelliferylphosphate; they also contained a factor that blocked superoxide anion production by human neutrophils stimulated with formyl-Met-Leu-Phe. The pH optimum of the enzyme was approximately 5.0. The level of phosphatase activity detected in several isolates of C. burnetii implicated in acute (Nine Mile) and chronic (S Q217, PRS Q177, K Q154) Q fever was 25 to 60 times greater than that reported in other microorganisms, including Leishmania and Legionella spp. The enzyme was found in rickettsiae grown in different hosts (L929 cells and embryonated eggs) and, in the case of L929 cells, for both short periods (less than a month) and the long term (years). Cytochemical techniques coupled with electron microscopy localized the phosphatase activity to the periplasmic gap in the parasite. Ion-exchange chromatography revealed a major species of the enzyme and showed that the enzyme of the parasite was distinct from that of the host cell (L929 fibroblasts); its apparent molecular weight was 74,000. Phosphatase inhibitors (i.e., molybdate heteropolyanions) had differential effects on the phosphatases of the parasite and host cell. C. burnetii supernatant fluid inhibited superoxide anion production by formyl-Met-Leu-Phe-stimulated human neutrophils; molybdate inhibitors reversed the inhibition. Treatment of C. burnetii-infected L929 cells with one of the molybdate compounds (complex B') significantly reduced the level of infection and did not affect the viability or growth of the host cell. These data suggest that the acid phosphatase of the parasite may be a major virulence determinant, allowing the agent to avoid being killed during uptake by phagocytes and subsequently in the phagolysosome.
Baca
O G
OG
Department of Biology, University of New Mexico, Albuquerque 87131.
Roman
M J
MJ
Glew
R H
RH
Christner
R F
RF
Buhler
J E
JE
Aragon
A S
AS
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016997:Coxiella burnetii / Q000201:enzymology* / Q000472:pathogenicity* / Q000648:ultrastructure; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007739:L Cells; D051379:Mice; D008970:Molecular Weight; D008982:Molybdenum / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology; D011778:Q Fever / Q000188:drug therapy; D016897:Respiratory Burst; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; C044659:molybdate; D008982:Molybdenum; D000135:Acid Phosphatase