2-Deoxy-D-glucose inhibits intracellular multiplication and promotes intracellular killing of Legionella pneumophila in A/J mouse macrophages

Abstract

Legionella pneumophila can grow intracellularly in A/J mouse macrophages. 2-Deoxy-D-glucose (2dG) (0.1, 1, and 10 mM) inhibited intracellular multiplication and promoted intracellular killing of L. pneumophila dose dependently when it was added to the culture medium of macrophage monolayers, whereas it did not inhibit the bacterial growth in buffered yeast extract broth, which was used for an L. pneumophila culture. The effect of 2dG was reversible because the surviving bacteria resumed intracellular multiplication after the washing away of 2dG from the culture. The effect of 2dG was also competitively inhibited by high concentrations of glucose. The inhibitory effect of 2dG was not attributed to the inhibition of bacterial phagocytosis by macrophages. Furthermore, sodium fluoride (0.1 and 1 mM), cycloheximide (0.1 and 1 μg/ml), and tunicamycin (1, 2, and 5 μg/ml) did not promote the killing of L. pneumophila in macrophages, implying that the inhibitory effect of 2dG cannot be attributed to the inhibition of glycolysis, protein synthesis, and protein glycosylation in macrophages. We suggest that 2dG promotes intracellular killing of L. pneumophila by activating some novel killing mechanism of macrophages.