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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Legionella pneumophila replicates within amoebae and macrophages and causes the severe pneumonia Legionnaires' disease. When broth cultures enter the post-exponential growth (PE) phase or experience amino acid limitation, L. pneumophila accumulates the stringent response signal (p)ppGpp and expresses traits likely to promote transmission to a new phagocyte. The hypothesis that a stringent response mechanism regulates L. pneumophila virulence was bolstered by our finding that the avirulent mutant Lp120 contains an internal deletion in the gene encoding the stationary phase sigma factor RpoS. To test directly whether RpoS co-ordinates virulence with stationary phase, isogenic wild-type, rpoS-120 and rpoS null mutant strains were constructed and analysed. PE phase L. pneumophila became cytotoxic by an RpoS-independent pathway, but their sodium sensitivity and maximal expression of flagellin required RpoS. Likewise, full induction of sodium sensitivity by experimentally induced (p)ppGpp synthesis required RpoS. To replicate efficiently in macrophages, L. pneumophila used both RpoS-dependent and -independent pathways. Like those containing the dotA type IV secretory apparatus mutant, phagosomes harbouring either rpoS or dotA rpoS mutants rapidly acquired the late endosomal protein LAMP-1, but not the lysosomal marker Texas red-ovalbumin. Together, the data support a model in which RpoS co-operates with other regulators to induce L. pneumophila virulence in the PE phase.
Mol Microbiol 2001 Jun
PMID:RpoS co-operates with other factors to induce Legionella pneumophila virulence in the stationary phase. 1140 23

Legionella pneumophila is the causative agent of Legionnaires' disease, a severe pneumonia. Dependent on the icm/dot loci, L. pneumophila survives and replicates in macrophages and amoebae within a specialized phagosome that does not fuse with lysosomes. Here, we report that phagocytosis of wild-type L. pneumophila is more efficient than uptake of icm/dot mutants. Compared with the wild-type strain JR32, about 10 times fewer icm/dot mutant bacteria were recovered from HL-60 macrophages in a gentamicin protection assay. The defect in phagocytosis of the mutants could be complemented by supplying the corresponding genes on a plasmid. Using fluorescence microscopy and green fluorescent protein (GFP)-expressing strains, 10-20 times fewer icm/dot mutant bacteria were found to be internalized by HL-60 cells and human monocyte-derived macrophages (HMMPhi). Compared with icm/dot mutants, wild-type L. pneumophila infected two to three times more macrophages and yielded a population of highly infected host cells (15-70 bacteria per macrophage) that was not observed with icm/dot mutant strains. Wild-type and icmT mutant bacteria were found to adhere similarly and compete for binding to HMMPhi. In addition, wild-type L. pneumophila was also phagocytosed more efficiently by Acanthamoeba castellanii, indicating that the process is independent of adherence receptor(s). Wild-type L. pneumophila enhanced phagocytosis of an icmT mutant strain in a synchronous co-infection, suggesting that increased phagocytosis results from (a) secreted effector(s) acting in trans.
Mol Microbiol 2001 Nov
PMID:Icm/dot-dependent upregulation of phagocytosis by Legionella pneumophila. 1172 29

Actin system of eukaryotic cells creates the driving force for alteration of the phagocytic cytoplasmatic membrane shape, which is needed for cell movement in the space and for microorganism capturing. Manipulation by actin cytoskeleton mediated through specialized bacterial products can promote proliferation of bacteria in the host. Published reports indicate that bacterial regulation of the actin system activity can be carried out by two modes: 1) by bacterial interactions with surface receptors regulating the cytoskeleton status and 2) by introduction of bacterial products targeted to the cytoskeleton components into the cells. Intracellular pathogens (Legionella) possess ligands which interact with eukaryotic receptors and type IV secretion system fit for translocation of heretofore unknown effector molecules into the cytoplasm. This can result in stimulation of actin polymerization activity and accelerated phagocytosis of the bacteria with rapid multiplication in tissues. By contrast, representatives of extracellular pathogens (Clostridium) produce substances penetrating inside the eukaryotic cells and destroying the actin network, thus making capturing and intracellular digestion of these microorganisms impossible.
Mol Gen Mikrobiol Virusol 2001
PMID:[Pathogenicity of bacteria and the actin cytoskeleton]. 1181 17

An 8-month-old girl with respiratory distress and stridor was admitted to our hospital. Two days later, she died of respiratory insufficiency due to pneumonia. Autopsy confirmed the presence of follicular bronchiolitis (FBB) in both lungs. After consideration of her clinical course, we focused on three pathogens: Legionella pneumophilia, Pneumocystis carinii, and Mycobacterium tuberculosis. Only Legionella pneumophilia was detected by both immunohistochemistry and polymerase chain reaction.
Pediatr Pathol Mol Med
PMID:Follicular bronchiolitis associated with Legionella pneumophilia infection. 1184 78

We have shown previously that the five rib (release of intracellular bacteria) mutants of Legionella pneumophila are competent for intracellular replication but defective in pore formation-mediated cytolysis and egress from protozoan and mammalian cells. The rib phenotype results from a point mutation (deletion) DeltaG544 in icmT that is predicted to result in the expression of a protein truncated by 32 amino acids from the C-terminus. In contrast to the rib mutants that are capable of intracellular replication, an icmT null mutant was completely defective in intracellular replication within mammalian and protozoan cells, in addition to its defect in pore formation-mediated cytolysis. The icmT wild-type allele complemented the icmT null mutant for both defects of intracellular replication and pore formation-mediated cytolysis and egress from mammalian cells. In contrast, the icmTDeltaG544 allele complemented the icmT null mutant for intracellular growth, but not for the pore-forming activity. Consistent with their defect in pore formation-mediated cytotoxicity in vitro, both mutants failed to cause pulmonary inflammation in A/J mice. Interestingly, the rib mutant was severely defective in intracellular growth within Acanthamoeba polyphaga. Confocal laser scanning and electron microscopy confirmed that the rib mutant and the icmT null mutant were severely and completely defective, respectively, in intracellular growth in A. polyphaga, and the respective defects correlated with fusion of the bacterial phagosomes to lysosomes. Taken together, the data showed that the C-terminus domain of IcmT is essential for the pore-forming activity and is required for intracellular trafficking and replication within A. polyphaga, but not within mammalian cells.
Mol Microbiol 2002 Mar
PMID:The C-terminus of IcmT is essential for pore formation and for intracellular trafficking of Legionella pneumophila within Acanthamoeba polyphaga. 1191 2

Type IV secretion systems (TFSS) mediate secretion or direct cell-to-cell transfer of virulence factors (proteins or protein-DNA complexes) from many Gram-negative animal, human and plant pathogens, such as Agrobacterium tumefaciens, Bartonella tribocorum, Bordetella pertussis, Brucella suis, Helicobacter pylori, Legionella pneumophila and Rickettsia prowazekii, into eukaryotic cells. Bacterial conjugation is also classified as a TFSS-like process mediating the spread of broad-host-range plasmids between Gram-negative bacteria such as RP4 and R388, which carry antibiotic resistance genes. Genetic, biochemical, cell biological and structural biology experiments led to significant progress in the understanding of several aspects of TFSS processes. X-ray crystallography revealed that homologues of the A. tumefaciens inner membrane-associated proteins VirB11 and VirD4 from H. pylori and R388, respectively, may form channels for substrate translocation or assembly of the transmembrane TFSS machinery. Biochemical and cell biological experiments revealed interactions between components of the periplasmic core components VirB8, VirB9 and VirB10, which may form the translocation channel. Analysis of A. tumefaciens virulence proteins VirE2 and VirF suggested that the periplasmic translocation route of the pertussis toxin from B. pertussis may be more generally valid than previously anticipated. Secretion and modification of toxins from H. pylori and L. pneumophila profoundly affect host cell metabolism, thus entering the discipline of cellular microbiology. Finally, results from genome sequencing projects revealed the presence of up to three TFSS in a single organism, and the analysis of their interplay and adaptation to different functions will be a future challenge. TFSS-carrying plasmids were discovered in different ecosystems, suggesting that genetic exchange may speed up their evolution and adaptation to different cell-cell interactions.
Mol Microbiol 2002 Mar
PMID:Bacterial secrets of secretion: EuroConference on the biology of type IV secretion processes. 1191 19

Pathogenic Legionella pneumophila evolved as a parasite of aquatic amoebae. To persist in the environment, the microbe must be proficient at both replication and transmission. In laboratory cultures, as nutrients become scarce a stringent response-like pathway coordinates exit from the exponential growth phase with induction of traits correlated with virulence, including motility. A screen for mutants that express the flagellin gene poorly identified five activators of virulence: LetA/LetS, a two-component regulator homologous to GacA/GacS of Pseudomonas and SirA/BarA of Salmonella; the stationary-phase sigma factor RpoS; the flagellar sigma factor FliA; and a new locus, letE. Unlike wild type, post-exponential-phase letA and letS mutants were not motile, cytotoxic, sodium sensitive or proficient at infecting macrophages. L. pneumophila also required fliA to become motile, cytotoxic and to infect macrophages efficiently and letE to express sodium sensitivity and maximal motility and cytotoxicity. When induced to express RelA, all of the strains exited the exponential phase, but only wild type converted to the fully virulent form. In contrast, intracellular replication was independent of letA, letS, letE or fliA. Together, the data indicate that, as the nutrient supply wanes, ppGpp triggers a regulatory cascade mediated by LetA/ LetS, RpoS, FliA and letE that coordinates differentiation of replicating L. pneumophila to a transmissible form.
Mol Microbiol 2002 Apr
PMID:A two-component regulator induces the transmission phenotype of stationary-phase Legionella pneumophila. 1196 72

An 8-month-old girl with respiratory distress and stridor was admitted to the authors' hospital. Two days later, she died of respiratory insufficiency due to pneumonia. Autopsy confirmed the presence of follicular bronchiolitis (FBB) in both lungs. After considering her clinical course, the authors focused on three pathogens: Legionella pneumophilia, Pneumocystis carinii, and Mycobacterium tuberculosis. Only Legionella pneumophilia was detected by both immunohistochemistry and PCR.
Pediatr Pathol Mol Med
PMID:Follicular bronchiolitis (FBB) associated with Legionella pneumophilia infection. 1253 68

Brazilian purpuric fever (BPF) is a fulminant septicaemic infection of young children, caused by a clonal group of strains of Haemophilus influenzae biogroup aegyptius (Hae), an organism previously solely associated with conjunctivitis. Their special capacity to invade from the initial site of conjunctival infection is unexplained. A polymerase chain reaction (PCR)-amplified subtractive hybridization technique was used to identify genes specific to the BPF clonal group. A copy of bacteriophage HP1 and 46 further chromosomal loci were identified in the BPF but not in the conjunctivitis strain of Hae. Sixteen were characterized further, and one - encoding an analogue of the Legionella pneumophila epithelial cell entry-enhancing protein EnhC - was investigated in depth. Two genes, bpf001 and bpf002, unique to the BPF clonal group were identified between homologues of HI1276 and HI1277 in a complex locus close to H. influenzae genetic island 1, recently identified in pathogenic H. influenzae type b. Bpf001 encodes a protein homologous to EnhC and to the previously uncharacterized product of the meningococcal gene NMB0419. Functional studies of bpf001 proving intractable, NMB0419 was chosen as a surrogate for investigation and shown to modulate bacterial interaction with monolayers of human respiratory epithelial cells, promoting invasion, the first stage (for Hae) in the pathogenesis of BPF.
Mol Microbiol 2003 Feb
PMID:Identification and characterization of genomic loci unique to the Brazilian purpuric fever clonal group of H. influenzae biogroup aegyptius: functionality explored using meningococcal homology. 1258 62

Legionella pneumophila establishes a replication vacuole within phagocytes that requires the bacterial Dot/Icm apparatus for its formation. This apparatus is predicted to translocate effectors into host cells. We hypothesized that some translocated proteins also function to maintain the integrity of the Dot/Icm translocator. Mutations that destroy this function are predicted to result in a Dot/Icm complex that poisons the bacterium, resulting in reduced viability. To identify such mutants, strains were isolated (called lid-) that showed reduced viability on bacteriological medium in the presence of an intact Dot/Icm apparatus, but which had high viability in the absence of the translocator. Several such mutants were analysed in detail to identify candidate strains that may have lost the ability to synthesize a translocated substrate of Dot/Icm. Two such strains had mutations in the lidA gene. The LidA protein exhibits properties expected for a translocated substrate of Dot/Icm that is important for maintenance of bacterial cell integrity: it associates with the phagosomal surface, promotes replication vacuole formation, and is important for both efficient intracellular growth and high viability on bacteriological media after introduction of a plasmid that allows high level expression of the dotA gene.
Mol Microbiol 2003 Apr
PMID:The Legionella pneumophila LidA protein: a translocated substrate of the Dot/Icm system associated with maintenance of bacterial integrity. 1267 93


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