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)

For the treatment of Legionella pneumophila infections erythromycin and rifampicin are the antibiotics of choice. In view of reported therapy failures other antibiotics, e.g. the quinolones, are currently under investigation. The sensitivity of L. pneumophila to four antibiotics and to combinations of antibiotics was investigated and the rate of mutations was calculated. For 20 L. pneumophila strains we determined the MIC of rifampicin (0.002-0.004 mg/l), erythromycin (0.063-0.125 mg/l), norfloxacin (0.125 mg/l) and ciprofloxacin (0.016-0.032 mg/l). Mutation rates ranged from 1 x 10(-8) for ciprofloxacin to greater than 1 x 10(-7) for erythromycin, resulting in high-level resistance to rifampicin in most strains and erythromycin resistance in one strain, but not in resistance to the quinolones. The combination of erythromycin and rifampicin was synergistic (FIC index less than 0.5) against four of the L. pneumophila strains and showed indifference (FIC index 0.5-2.0) for the remainder (mean FIC index 0.79). Combinations of ciprofloxacin and erythromycin and of rifampicin and ciprofloxacin showed only indifference (mean FIC index respectively 1.05 and 1.21). Combining rifampicin with ciprofloxacin was not effective in reducing the number of mutants for either of these antibiotics, whereas the other combinations did prevent this.
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PMID:Sensitivity and resistance of Legionella pneumophila to some antibiotics and combinations of antibiotics. 320 75

In vitro infection of macrophages with Legionella pneumophila induced interleukin-1alpha (IL-1alpha), IL-10, monocyte chemotactic protein 1 (MCP-1), and MCP-3 but not IL-12. The lipopolysaccharide (LPS)-induced production of IL-12 was down-regulated by infection with virulent L. pneumophila, but other cytokines were not affected. In contrast, avirulent L. pneumophila or UV-killed, virulent L. pneumophila did not induce any suppression of IL-12. The IL-12 suppression occurred at the level of mRNA accumulation for IL-12 genes in response to LPS stimulation, but the infection induced a marked accumulation of mRNA for both MCP-1 and MCP-3, which are known to suppress IL-12 production in LPS-stimulated macrophages. However, pretreatment of macrophages with MCP-1 did not suppress LPS-induced IL-12 production at the concentrations induced by L. pneumophila infection. These results suggest that L. pneumophila selectively suppresses IL-12 production induced by LPS from macrophages in vitro by an MCP-independent mechanism.
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PMID:Legionella pneumophila suppresses interleukin-12 production by macrophages. 1117 77

Proteins containing FIC (filamentation induced by cyclic adenosine monophosphate) domains are found in both prokaryotic and eukaryotic organisms, but their function has remained elusive. Recent studies indicate that bacterial FIC domain-containing proteins disrupt host cell processes after being delivered into eukaryotic host cells: The Vibrio parahaemolyticus VopS protein interferes with Rho guanine triphosphatase (GTPase) function, and the Legionella pneumophila AnkX protein disrupts the microtubule-dependent transport of vesicles. Analysis of the VopS protein revealed that the FIC domain covalently modifies Rac by transferring adenosine 5'-monophosphate (AMP) to a threonine residue in the switch 1 region of the protein. Thus, FIC domain-mediated AMPylation is involved in the posttranslational regulation of protein function, and this activity has been subverted by microbial pathogens to modulate cellular functions during infection.
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PMID:Bacterial FIC Proteins AMP Up Infection. 1929 28

The intracellular pathogen Legionella pneumophila modulates the activity of host GTPases to direct the transport and assembly of the membrane-bound compartment in which it resides. In vitro studies have indicated that the Legionella protein DrrA post-translationally modifies the GTPase Rab1 by a process called AMPylation. Here we used mass spectrometry to investigate post-translational modifications to Rab1 that occur during infection of host cells by Legionella. Consistent with in vitro studies, DrrA-mediated AMPylation of a conserved tyrosine residue in the switch II region of Rab1 was detected during infection. In addition, a modification to an adjacent serine residue in Rab1 was discovered, which was independent of DrrA. The Legionella effector protein AnkX was required for this modification. Biochemical studies determined that AnkX directly mediates the covalent attachment of a phosphocholine moiety to Rab1. This phosphocholine transferase activity used CDP-choline as a substrate and required a conserved histidine residue located in the FIC domain of the AnkX protein. During infection, AnkX modified both Rab1 and Rab35, which explains how this protein modulates membrane transport through both the endocytic and exocytic pathways of the host cell. Thus, phosphocholination of Rab GTPases represents a mechanism by which bacterial FIC-domain-containing proteins can alter host-cell functions.
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PMID:Modulation of Rab GTPase function by a protein phosphocholine transferase. 2184 63

The FIC motif and the eukaryotic-like ankyrin repeats are found in many bacterial type IV effectors, yet little is known about how these domains enable bacteria to modulate host cell functions. Bacterial FIC domains typically bind ATP and transfer adenosine monophosphate moiety onto target proteins. The ankyrin repeat-containing protein AnkX encoded by the intracellular pathogen Legionella pneumophila is unique in that its FIC domain binds to CDP-choline and transfers a phosphocholine residue onto proteins in the Rab1 GTPase family. By determining the structures of unbound AnkX and AnkX with bound CDP-choline, CMP/phosphocholine and CMP, we demonstrate that the orientation of substrate binding in relation to the catalytic FIC motif enables this protein to function as a phosphocholinating enzyme rather than a nucleotidyl transferase. Additionally, the structure reveals that the ankyrin repeats mediate scaffolding interactions that resemble those found in protein-protein interactions, but are unprecedented in intramolecular interactions. Together with phosphocholination experiments, our structures unify a general phosphoryl transferase mechanism common to all FIC enzymes that should be conserved from bacteria to human.
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PMID:Structure of the Legionella effector AnkX reveals the mechanism of phosphocholine transfer by the FIC domain. 2357 77