Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five 14C-labelled macrolide antibiotics (erythromycin, josamycin, clarithromycin (TE-031), rokitamycin and roxithromycin) were studied for their transport into human polymorphonuclear leucocytes. Intracellular/extracellular concentration ratios (transport ratios) of these macrolides were quite high: erythromycin, 6.6; josamycin, 15.5; clarithromycin, 16.4; rokitamycin, 30.5; and roxithromycin, 21.9. When polymorphonuclear leucocytes were pre-treated with formaldehyde or incubated at 4 degrees C, or at low pH, transport ratios were reduced. When extracellular macrolide was removed, intracellular macrolide concentrations became as low as 30% of the pre-wash concentrations in 5 min. KF lowered the transport ratios of josamycin and rokitamycin in particular and NaCN reduced the transport ratios of erythromycin and josamycin strikingly. Ouabain slightly lowered transport ratios of all the antibiotics tested except roxithromycin, and 2, 4-dinitrophenol decreased the transport ratio of clarithromycin markedly. The addition of various amino acids or hexose did not inhibit the transfer. Adenosine, however, inhibited the transfer of these antibiotics except erythromycin and lowered transport ratios by 83 to 92%. Puromycin reduced transport ratios of the same antibiotics by 59 to 95%. With polymorphonuclear leucocytes that had phagocytosed Legionella pneumophila serogroup 1, transport ratios of all five drugs tended to decrease. However, when Staphylococcus aureus ATCC 25923 or opsonized zymosan was phagocytosed, transport ratios for macrolides, except for roxithromycin, increased.
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PMID:Penetration of macrolides into human polymorphonuclear leucocytes. 259 96

The effect of Legionella pneumophila toxin on selected functions of human polymorphonuclear leukocytes was investigated. Amounts of L. pneumophila toxin that had no effect on leukocyte viability or phagocytosis significantly decreased hexose monophosphate shunt activity and O2 consumption during phagocytosis and bacterial iodination and killing in a dose-dependent fashion. The mechanism of action of this toxin appears to be unique among bacterial products thus far studied.
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PMID:The effects of Legionella pneumophila toxin on oxidative processes and bacterial killing of human polymorphonuclear leukocytes. 705 Feb 55

Toll-like receptor (TLR) stimulation induces a pronounced shift to increased glycolytic metabolism in mammalian macrophages. We observed that bone marrow-derived macrophages (BMMs) increase glycolysis in response to infection with Legionella pneumophila, but the role of host macrophage glycolysis in terms of intracellular L. pneumophila replication is not currently understood. Treatment with 2-deoxyglucose (2DG) blocks L. pneumophila replication in mammalian macrophages but has no effect on bacteria grown in broth. In addition, we found that 2DG had no effect on bacteria grown in amoebae. We used a serial enrichment strategy to reveal that the effect of 2DG on L. pneumophila in macrophages requires the L. pneumophila hexose-phosphate transporter UhpC. Experiments with UhpC-deficient L. pneumophila revealed that mutant bacteria are also resistant to growth inhibition following treatment with phosphorylated 2DG in broth, suggesting that the inhibitory effect of 2DG on L. pneumophila in mammalian cells requires 2DG phosphorylation. UhpC-deficient L. pneumophila replicates without a growth defect in BMMs and protozoan host cells and also replicates without a growth defect in BMMs treated with 2DG. Our data indicate that neither TLR signaling-dependent increased macrophage glycolysis nor inhibition of macrophage glycolysis has a substantial effect on intracellular L. pneumophila replication. These results are consistent with the view that L. pneumophila can employ diverse metabolic strategies to exploit its host cells.IMPORTANCE 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 of L. pneumophila during infection of macrophages, leading to speculation that L. pneumophila may exploit macrophage glycolysis. We isolated L. pneumophila mutants resistant to the inhibitory effect of 2DG in macrophages, identifying a L. 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 of L. pneumophila, which is consistent with a view of L. pneumophila as a metabolic generalist.
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PMID:Legionella pneumophila Is Directly Sensitive to 2-Deoxyglucose-Phosphate via Its UhpC Transporter but Is Indifferent to Shifts in Host Cell Glycolytic Metabolism. 2978 86