Legionella pneumophila: an aquatic microbe goes astray.

Legionella pneumophila is naturally found in fresh water were the bacteria parasitize within protozoa. It also survives planctonically in water or biofilms. Upon aerosol formation via man-made water systems, L. pneumophila can enter the human lung and cause a severe form of pneumonia, called Legionnaires' disease. The pathogenesis of Legionnaires' disease is largely due to the ability of L. pneumophila to invade and grow within macrophages. An important characteristic of the intracellular survival strategy is the replication within the host vacuole that does not fuse with endosomes or lysosomes. In recent times a great number of bacterial virulence factors which affect growth of L. pneumophila in both macrophages and protozoa have been identified. The ongoing Legionella genome project and the use of genetically tractable surrogate hosts are expected to significantly contribute to the understanding of bacterium-host interactions and the regulation of virulence traits during the infection cycle. Since person-to-person transmission of legionellosis has never been observed, the measures for disease prevention have concentrated on eliminating the pathogen from water supplies. In this respect detection and analysis of Legionella in complex environmental consortia become increasingly important. With the availability of new molecular tools this area of applied research has gained new momentum.

[1]  E. White,et al.  Attachment and entry of Legionella pneumophila in Hartmannella vermiformis. , 1993, The Journal of infectious diseases.

[2]  J. Hacker,et al.  Influence of site specifically altered Mip proteins on intracellular survival of Legionella pneumophila in eukaryotic cells , 1995, Infection and immunity.

[3]  E. Ingham,et al.  Survival and Growth of Burkholderia cepacia Within the Free-Living Amoeba Acanthamoeba polyphaga , 2000, European Journal of Clinical Microbiology and Infectious Diseases.

[4]  S. Berk,et al.  Production of Respirable Vesicles Containing LiveLegionella pneumophila Cells by TwoAcanthamoeba spp , 1998, Applied and Environmental Microbiology.

[5]  S. Stevanović,et al.  Novel Lysophospholipase A Secreted byLegionella pneumophila , 2001, Journal of bacteriology.

[6]  W. Dowdle,et al.  Legionnaires' disease: isolation of a bacterium and demonstration of its role in other respiratory disease. , 1977, The New England journal of medicine.

[7]  R. J. Gibson,et al.  Charcoal-yeast extract agar: primary isolation medium for Legionella pneumophila , 1979, Journal of clinical microbiology.

[8]  W. Winn,et al.  Legionnaires disease: historical perspective , 1988, Clinical Microbiology Reviews.

[9]  J Hacker,et al.  Common molecular mechanisms of symbiosis and pathogenesis. , 2000, Trends in microbiology.

[10]  W. Ludwig,et al.  Interaction of Legionella pneumophila with Dictyostelium discoideum , 2002 .

[11]  J Hacker,et al.  Regrowth of Legionella pneumophila in a heat-disinfected plumbing system. , 1998, Zentralblatt fur Bakteriologie : international journal of medical microbiology.

[12]  J. Russo,et al.  Relationships between a new type IV secretion system and the icm/dot virulence system of Legionella pneumophila , 1999, Molecular microbiology.

[13]  L. Bermudez,et al.  Legionella pneumophila Entry GenertxA Is Involved in Virulence , 2001, Infection and Immunity.

[14]  J. Feeley,et al.  Pontiac fever: isolation of the etiologic agent (Legionella pneumophilia) and demonstration of its mode of transmission. , 1981, American journal of epidemiology.

[15]  N. Cianciotto,et al.  Iron Requirements of and Acquisition of Iron by Legionella pneumophila , 2002 .

[16]  N. Engleberg,et al.  Protein expression by the protozoan Hartmannella vermiformis upon contact with its bacterial parasite Legionella pneumophila , 1994, Infection and immunity.

[17]  W. Johnson,et al.  Legionella pneumophila lipopolysaccharide activates the classical complement pathway , 1992, Infection and immunity.

[18]  O. Harb,et al.  Invasion of Protozoa by Legionella pneumophila and Its Role in Bacterial Ecology and Pathogenesis , 1998, Applied and Environmental Microbiology.

[19]  R. Atlas Legionella: from environmental habitats to disease pathology, detection and control. , 1999, Environmental microbiology.

[20]  J. Mege,et al.  Legionella pneumophila inhibits superoxide generation in human monocytes via the down‐modulation of α and β protein kinase C isotypes , 1994 .

[21]  M. R. Brown,et al.  Unexplored reservoirs of pathogenic bacteria: protozoa and biofilms. , 1999, Trends in microbiology.

[22]  M. Rohde,et al.  Chromosomal insertion and excision of a 30 kb unstable genetic element is responsible for phase variation of lipopolysaccharide and other virulence determinants in Legionella pneumophila. , 2001, Molecular microbiology.

[23]  F. Ausubel,et al.  Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  U. Göbel,et al.  Cloning and characterization of a Legionella pneumophila-specific gene encoding a member of the LysR family of transcriptional regulators , 2000, Molecular and General Genetics MGG.

[25]  S. Berk,et al.  Adaptation of amoebae to cooling tower biocides , 1994, Microbial Ecology.

[26]  M. Rohde,et al.  Chromosomal insertion and excision of a 30 kb unstable genetic element is responsible for phase variation of lipopolysaccharide and other virulence determinants in Legionella pneumophila , 2001 .

[27]  Rowbotham Tj,et al.  Current views on the relationships between amoebae, legionellae and man. , 1986 .

[28]  L. Pine,et al.  Amino acid requirements of Legionella pneumophila , 1980, Journal of clinical microbiology.

[29]  S. Berk,et al.  Stimulatory effect of cooling tower biocides on amoebae , 1993, Applied and environmental microbiology.

[30]  J. Mcdade,et al.  Pathologic findings in guinea pigs inoculated intraperitoneally with the Legionnaires' disease bacterium. , 1979, Annals of Internal Medicine.

[31]  S. Donnellan,et al.  Interspecies sequence differences in the Mip protein from the genus Legionella: implications for function and evolutionary relatedness , 1997, Molecular microbiology.

[32]  O. Harb,et al.  Utilization of similar mechanisms by Legionella pneumophila to parasitize two evolutionarily distant host cells, mammalian macrophages and protozoa , 1997, Infection and immunity.

[33]  B. Stone,et al.  Expression of Multiple Pili by Legionella pneumophila: Identification and Characterization of a Type IV Pilin Gene and Its Role in Adherence to Mammalian and Protozoan Cells , 1998, Infection and Immunity.

[34]  Y. Kwaik,et al.  Fatal attraction of mammalian cells to Legionella pneumophila , 1998, Molecular microbiology.

[35]  E. Hickey,et al.  A Legionella pneumophila gene that promotes hemin binding , 1996, Infection and immunity.

[36]  K. Schleifer,et al.  Specific Detection of Legionella pneumophila: Construction of a New 16S rRNA-Targeted Oligonucleotide Probe , 1998, Applied and Environmental Microbiology.

[37]  K. Schleifer,et al.  Development of 18S rRNA-targeted oligonucleotide probes for specific detection of Hartmannella and Naegleria in Legionella-positive environmental samples. , 2001, Systematic and applied microbiology.

[38]  T. Steele,et al.  Infection of Tetrahymena pyriformis by Legionella longbeachae and other Legionella species found in potting mixes , 1996, Applied and environmental microbiology.

[39]  J. Kurtz,et al.  Antigenic lipopolysaccharide components of Legionella pneumophila recognized by monoclonal antibodies: possibilities and limitations for division of the species into serogroups , 1997, Journal of clinical microbiology.

[40]  M. R. Brown,et al.  Relationship between Legionella pneumophila and Acanthamoeba polyphaga: Physiological Status and Susceptibility to Chemical Inactivation , 1992, Applied and environmental microbiology.

[41]  J. Hacker,et al.  Characterization of legiolysin (lly), responsible for haemolytic activity, colour production and fluorescence of Legionella pneumophila , 1991, Molecular microbiology.

[42]  B. Neumeister,et al.  Secreted Enzymatic Activities of Wild-Type andpilD-Deficient Legionella pneumophila , 2000, Infection and Immunity.

[43]  M. Liles,et al.  Discovery of a Nonclassical Siderophore, Legiobactin, Produced by Strains of Legionella pneumophila , 2000, Journal of bacteriology.

[44]  C. Lück,et al.  Characterization of a 16-Kilodalton Species-Specific Protein of Legionella pneumophila Promoting Uptake in Amoebae , 2002 .

[45]  M. Maiwald,et al.  Laboratory methods for the diagnosis of Legionella infections , 1998 .

[46]  W. Johnson,et al.  Acquisition of iron by Legionella pneumophila: role of iron reductase , 1991, Infection and immunity.

[47]  Y. Kwaik,et al.  Identification of a Gal/GalNAc Lectin in the Protozoan Hartmannella vermiformis as a Potential Receptor for Attachment and Invasion by the Legionnaires' Disease Bacterium , 1997, The Journal of experimental medicine.

[48]  C. Keevil,et al.  Influence of temperature and plumbing material selection on biofilm formation and growth of Legionella pneumophila in a model potable water system containing complex microbial flora , 1994, Applied and environmental microbiology.

[49]  E. White,et al.  Effects of cytochalasin D and methylamine on intracellular growth of Legionella pneumophila in amoebae and human monocyte-like cells , 1991, Infection and immunity.

[50]  N. Cianciotto,et al.  Legionella pneumophila Major Acid Phosphatase and Its Role in Intracellular Infection , 2001, Infection and Immunity.

[51]  Breiman Rf,et al.  Legionnaires' disease: clinical, epidemiological, and public health perspectives. , 1998, Seminars in respiratory infections.

[52]  M. Poch,et al.  Ferric reductases of Legionella pneumophila , 2004, Biometals.

[53]  H. Shuman,et al.  Legionella pneumophila Contains a Type II General Secretion Pathway Required for Growth in Amoebae as Well as for Secretion of the Msp Protease , 1999, Infection and Immunity.

[54]  O. Harb,et al.  From protozoa to mammalian cells: a new paradigm in the life cycle of intracellular bacterial pathogens. , 2000, Environmental microbiology.

[55]  P. Edelstein Comparative study of selective media for isolation of Legionella pneumophila from potable water , 1982, Journal of clinical microbiology.

[56]  M. S. McClain,et al.  The role of Legionella pneumophila-infected Hartmannella vermiformis as an infectious particle in a murine model of Legionnaire's disease , 1997, Infection and immunity.

[57]  O. Harb,et al.  Signal Transduction in the Protozoan HostHartmannella vermiformis upon Attachment and Invasion byLegionella micdadei , 1998, Applied and Environmental Microbiology.

[58]  Y. Yamaguchi,et al.  Disinfectant effects of hot water, ultraviolet light, silver ions and chlorine on strains of Legionella and nontuberculous mycobacteria. , 2000, Microbios.

[59]  D. White,et al.  Detection of Legionella pneumophila in biofilms containing a complex microbial consortium by gas chromatography-mass spectrometry analysis of genus-specific hydroxy fatty acids. , 1993, FEMS Microbiology Letters.

[60]  T. Byrd,et al.  Aberrantly low transferrin receptor expression on human monocytes is associated with nonpermissiveness for Legionella pneumophila growth. , 2000, The Journal of infectious diseases.

[61]  Y. Kwaik,et al.  The use of differential display‐PCR to isolate and characterize a Legionella pneumophila locus induced during the intracellular infection of macrophages , 1996, Molecular microbiology.

[62]  M. Swanson,et al.  Legionella pneumophila pathogesesis: a fateful journey from amoebae to macrophages. , 2000, Annual review of microbiology.

[63]  K. Heuner,et al.  The expression of the flagellum of Legionella pneumophila is modulated by different environmental factors. , 1999, FEMS microbiology letters.

[64]  K. Schleifer,et al.  In Situ Detection of Novel Bacterial Endosymbionts of Acanthamoeba spp. Phylogenetically Related to Members of the Order Rickettsiales , 1999, Applied and Environmental Microbiology.

[65]  Michael William Heuzenroeder,et al.  A mutation in an ompR-like gene on a Legionella longbeachae serogroup 1 plasmid attenuates virulence. , 2002, International journal of medical microbiology : IJMM.

[66]  M. Šuša,et al.  Heterogeneity in intracellular replication and cytopathogenicity of Legionella pneumophila and Legionella micdadei in mammalian and protozoan cells. , 1999, Microbial pathogenesis.

[67]  B. Fields,et al.  Classification of the genus Legionella. , 1998, Seminars in respiratory infections.

[68]  David A. D'Argenio,et al.  Drosophilaas a Model Host forPseudomonas aeruginosaInfection , 2001, Journal of bacteriology.

[69]  Y. Kwaik,et al.  The mechanism of killing and exiting the protozoan host Acanthamoeba polyphaga by Legionella pneumophila. , 2000, Environmental microbiology.

[70]  J. Cardelli,et al.  Intracellular Growth of Legionella pneumophila in Dictyostelium discoideum, a System for Genetic Analysis of Host-Pathogen Interactions , 2000, Infection and Immunity.

[71]  N. Cianciotto,et al.  The Legionella pneumophila iraAB Locus Is Required for Iron Assimilation, Intracellular Infection, and Virulence , 2000, Infection and Immunity.

[72]  S. Falkow,et al.  Growth of Legionella pneumophila in Acanthamoeba castellanii enhances invasion , 1994, Infection and immunity.

[73]  J. Hacker,et al.  Legionella pneumophila kills human phagocytes but not protozoan host cells by inducing apoptotic cell death. , 1998, FEMS microbiology letters.

[74]  H. Shuman,et al.  Intracellular multiplication and human macrophage killing by Legionella pneumophila are inhibited by conjugal components of IncQ plasmid RSF1010 , 1998, Molecular microbiology.

[75]  O. Harb,et al.  Heterogeneity in the Attachment and Uptake Mechanisms of the Legionnaires’ Disease Bacterium, Legionella pneumophila, by Protozoan Hosts , 1998, Applied and Environmental Microbiology.

[76]  K. Heuner,et al.  Function and Expression of Legionella pneumophila Surface Factors , 2002 .

[77]  P. Proksch,et al.  The Lly protein is essential for p-hydroxyphenylpyruvate dioxygenase activity in Legionella pneumophila. , 2001, FEMS microbiology letters.

[78]  U. Zähringer,et al.  Cloning and functional characterization of a 30 kb gene locus required for lipopolysaccharide biosynthesis in Legionella pneumophila. , 2000, International journal of medical microbiology : IJMM.

[79]  K. Schleifer,et al.  Microbiological safety of drinking water. , 2000, Annual review of microbiology.

[80]  N. Cianciotto,et al.  Genetics and molecular pathogenesis of Legionella pneumophila, an intracellular parasite of macrophages. , 1989, Molecular biology & medicine.

[81]  J. Hacker,et al.  Characterization of the Legionella pneumophila gene ligA. , 2000, International journal of medical microbiology : IJMM.

[82]  Y. Abu Kwaik,et al.  Activation of Caspase 3 during Legionella pneumophila-Induced Apoptosis , 1999, Infection and Immunity.

[83]  C. Fliermans,et al.  Ecological distribution of Legionella pneumophila , 1981, Applied and environmental microbiology.

[84]  K. Heuner,et al.  Cloning and genetic characterization of the flagellum subunit gene (flaA) of Legionella pneumophila serogroup 1 , 1995, Infection and immunity.

[85]  P. Lambert,et al.  Influence of intra-amoebic and other growth conditions on the surface properties of Legionella pneumophila , 1993, Infection and immunity.

[86]  M. Wagner,et al.  Various bacterial pathogens and symbionts infect the amoeba Dictyostelium discoideum. , 2002, International journal of medical microbiology : IJMM.

[87]  H. Scaife,et al.  Intraphagocytic growth induces an antibiotic-resistant phenotype of Legionella pneumophila , 1995, Antimicrobial agents and chemotherapy.

[88]  J. Hacker,et al.  The Lly protein protects Legionella pneumophila from light but does not directly influence its intracellular survival in Hartmannella vermiformis , 1995, Applied and environmental microbiology.

[89]  J. Hacker,et al.  Symbiosis and Pathogenesis: Evolution of the Microbe-Host Interaction , 2000, Naturwissenschaften.

[90]  J. Barbaree,et al.  Virulence of a Legionella anisa strain associated with Pontiac fever: an evaluation using protozoan, cell culture, and guinea pig models , 1990, Infection and immunity.

[91]  O. Harb,et al.  Identification of Macrophage-Specific Infectivity Loci (mil) of Legionella pneumophila That Are Not Required for Infectivity of Protozoa , 1998, Infection and Immunity.

[92]  Benson Rf,et al.  Classification of the genus Legionella. , 1998 .

[93]  K. Birkness,et al.  Mycobacterium avium Bacilli Grow Saprozoically in Coculture with Acanthamoeba polyphaga and Survive within Cyst Walls , 1998, Applied and Environmental Microbiology.

[94]  B. Fields,et al.  The molecular ecology of legionellae. , 1996, Trends in microbiology.

[95]  M. Horwitz,et al.  Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors , 1987, The Journal of experimental medicine.

[96]  R. Colwell,et al.  Viable Legionella pneumophila Not Detectable by Culture on Agar Media , 1987, Bio/Technology.

[97]  J. Hacker,et al.  Studies on the uptake and intracellular replication of Legionella pneumophila in protozoa and in macrophage-like cells , 1994 .

[98]  P. Valenti,et al.  Metal complexes of lactoferrin and their effect on the intracellular multiplication of Legionella pneumophila , 2000, Biometals.

[99]  M. Swanson,et al.  Co‐ordination of Legionella pneumophila virulence with entry into stationary phase by ppGpp , 1999, Molecular microbiology.

[100]  P. Hoffman,et al.  Legionella pneumophila htpAB heat shock operon: nucleotide sequence and expression of the 60-kilodalton antigen in L. pneumophila-infected HeLa cells , 1990, Infection and immunity.

[101]  E. Hickey,et al.  An iron- and fur-repressed Legionella pneumophila gene that promotes intracellular infection and encodes a protein with similarity to the Escherichia coli aerobactin synthetases , 1997, Infection and immunity.

[102]  N. Cianciotto,et al.  Legionella pneumophila mutants that are defective for iron acquisition and assimilation and intracellular infection , 1996, Infection and immunity.

[103]  P. Manning,et al.  Sequence-Based Classification Scheme for the GenusLegionella Targeting the mip Gene , 1998, Journal of Clinical Microbiology.

[104]  B. Fields The Social Life of Legionellae , 2002 .

[105]  M. Schleicher,et al.  Dictyostelium discoideum: a new host model system for intracellular pathogens of the genus Legionella , 2000, Cellular microbiology.

[106]  H. Shuman,et al.  Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[107]  P. Dejong,et al.  The Legionella pneumophila Sequencing Project , 2002 .

[108]  C. B. Fliermans,et al.  Ecology of Legionella: From data to knowledge with a little wisdom , 1996, Microbial Ecology.

[109]  S. Zink,et al.  Temporal Pore Formation-Mediated Egress from Macrophages and Alveolar Epithelial Cells by Legionella pneumophila , 2000, Infection and Immunity.

[110]  M. Collins Legionella infections in animals. , 1986, Israel journal of medical sciences.

[111]  J. Hacker,et al.  Temperature-dependent expression of flagella in Legionella. , 1991, Journal of general microbiology.

[112]  J. Hacker,et al.  Genome analysis of Legionella ssp. by orthogonal field alternation gel electrophoresis (OFAGE). , 1990, FEMS microbiology letters.

[113]  H. Shuman,et al.  The Legionella pneumophila rpoS Gene Is Required for Growth within Acanthamoeba castellanii , 1999, Journal of bacteriology.

[114]  ScienceDirect FEMS microbiology reviews , 1993 .

[115]  K. Heuner,et al.  Flagellum of Legionella pneumophilaPositively Affects the Early Phase of Infection of Eukaryotic Host Cells , 2001, Infection and Immunity.

[116]  Y. Kwaik,et al.  Identification of Putative Cytoskeletal Protein Homologues in the Protozoan Host Hartmannella vermiformis as Substrates for Induced Tyrosine Phosphatase Activity upon Attachment to the Legionnaires' Disease Bacterium, Legionella pneumophila , 1998, The Journal of experimental medicine.

[117]  M. Steinert,et al.  Immunolocalization of the Mip protein of intracellularly and extracellularly grown Legionella pneumophila , 2001, Letters in applied microbiology.

[118]  W. Goebel,et al.  Expression and use of the green fluorescent protein as a reporter system in Legionella pneumophila , 2000, Molecular and General Genetics MGG.

[119]  J. Pruckler,et al.  Legionella drozanskii sp. nov., Legionella rowbothamii sp. nov. and Legionella fallonii sp. nov.: three unusual new Legionella species. , 2001, International journal of systematic and evolutionary microbiology.

[120]  J. Coers,et al.  Modulation of phagosome biogenesis by Legionella pneumophila creates an organelle permissive for intracellular growth , 1999, Nature Cell Biology.

[121]  C. Broome,et al.  LEGIONNAIRES' DISEASE IN A PREPAID MEDICAL-CARE GROUP IN SEATTLE 1963-75 , 1979, The Lancet.

[122]  R. Amann,et al.  Identification and in situ detection of intracellular bacteria in the environment. , 2000, Sub-cellular biochemistry.

[123]  S. Kilvington,et al.  Survival of Legionella pneumophila within cysts of Acanthamoeba polyphaga following chlorine exposure. , 1990, The Journal of applied bacteriology.

[124]  J. Hacker,et al.  Crystal structure of Mip, a prolylisomerase from Legionella pneumophila , 2001, Nature Structural Biology.

[125]  J. Mege,et al.  Legionella pneumophila inhibits superoxide generation in human monocytes via the down-modulation of alpha and beta protein kinase C isotypes. , 1994, Journal of leukocyte biology.

[126]  R. Marre,et al.  Overexpresssion of a Legionella pneumophila homologue of the E. coli regulator csrA affects cell size, flagellation, and pigmentation. , 2001, International journal of medical microbiology : IJMM.

[127]  R Amann,et al.  Resuscitation of viable but nonculturable Legionella pneumophila Philadelphia JR32 by Acanthamoeba castellanii , 1997, Applied and environmental microbiology.

[128]  V. Yu,et al.  Community-acquired Legionnaires' disease. , 1989, Seminars in respiratory infections.