Legionella pneumophila Is Directly Sensitive to 2-Deoxyglucose-Phosphate via Its UhpC Transporter but Is Indifferent to Shifts in Host Cell Glycolytic Metabolism

We explored the relationship between macrophage glycolysis and replication of an intracellular bacterial pathogen,Legionella pneumophila . Previous studies demonstrated that a glycolysis inhibitor, 2-deoxyglucose (2DG), blocks replication ofL. pneumophila during infection of macrophages, leading to speculation thatL. pneumophila may exploit macrophage glycolysis. We isolatedL. pneumophila mutants resistant to the inhibitory effect of 2DG in macrophages, identifying aL. pneumophila hexose-phosphate transporter, UhpC, that is required for bacterial sensitivity to 2DG during infection. Our results reveal how a bacterial transporter mediates the direct antimicrobial effect of a toxic metabolite. Moreover, our results indicate that neither induction nor impairment of host glycolysis inhibits intracellular replication ofL. pneumophila , which is consistent with a view ofL. pneumophila as a metabolic generalist.