View Item 

Show simple item record

Legionella pneumophila couples fatty acid flux to microbial differentiation and virulence

dc.contributor.authorEdwards, Rachel L.en_US
dc.contributor.authorDalebroux, Zachary D.en_US
dc.contributor.authorSwanson, Michele S.en_US
dc.date.accessioned2010-06-01T20:58:06Z
dc.date.available2010-06-01T20:58:06Z
dc.date.issued2009-03en_US
dc.identifier.citationEdwards, Rachel L.; Dalebroux, Zachary D.; Swanson, Michele S. (2009). " Legionella pneumophila couples fatty acid flux to microbial differentiation and virulence." Molecular Microbiology 71(5): 1190-1204. <http://hdl.handle.net/2027.42/74062>en_US
dc.identifier.issn0950-382Xen_US
dc.identifier.issn1365-2958en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/74062
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=19170883&dopt=citationen_US
dc.description.abstractDuring its life cycle, Legionella pneumophila alternates between at least two phenotypes: a resilient, infectious form equipped for transmission and a replicative cell type that grows in amoebae and macrophages. Considering its versatility, we postulated that multiple cues regulate L. pneumophila differentiation. Beginning with a Biolog Phenotype MicroArray screen, we demonstrate that excess short-chain fatty acids (SCFAs) trigger replicative cells to cease growth and activate their panel of transmissive traits. To co-ordinate their response to SCFAs, L. pneumophila utilizes the LetA/LetS two-component system, but not phosphotransacetylase or acetyl kinase, two enzymes that generate high-energy phosphate intermediates. Instead, the stringent response enzyme SpoT appears to monitor fatty acid biosynthesis to govern transmission trait expression, as an altered distribution of acylated acyl carrier proteins correlated with the SpoT-dependent differentiation of cells treated with either excess SCFAs or the fatty acid biosynthesis inhibitors cerulenin and 5-(tetradecyloxy)-2-furoic acid. We postulate that, by exploiting the stringent response pathway to couple cellular differentiation to its metabolic state, L. pneumophila swiftly acclimates to stresses encountered in its host or the environment, thereby enhancing its overall fitness.en_US
dc.format.extent513563 bytes
dc.format.extent3109 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.publisherBlackwell Publishing Ltden_US
dc.rightsJournal compilation © 2009 Blackwell Publishingen_US
dc.titleLegionella pneumophila couples fatty acid flux to microbial differentiation and virulenceen_US
dc.typeArticleen_US
dc.subject.hlbsecondlevelMicrobiology and Immunologyen_US
dc.subject.hlbtoplevelScienceen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.en_US
dc.contributor.affiliationotherCellular and Molecular Biology Program anden_US
dc.identifier.pmid19170883en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/74062/1/j.1365-2958.2008.06593.x.pdf
dc.identifier.doi10.1111/j.1365-2958.2008.06593.xen_US
dc.identifier.sourceMolecular Microbiologyen_US
dc.identifier.citedreferenceAbdelrahman, Y.M., and Belland, R.J. ( 2005 ) The Chlamydial developmental cycle. FEMS Microbiol Rev 29: 949 – 959.en_US
dc.identifier.citedreferenceAlli, O.A.T., Gao, L.-Y., Pedersen, L.L., Zink, S., Radulic, M., Doric, M., and Abu Kwaik, Y. ( 2000 ) Temporal pore formation-mediated egress from macrophages and alveolar epithelial cells by Legionella pneumophila. Infect Immun 68: 6431 – 6440.en_US
dc.identifier.citedreferenceArchuleta, R.J., Hoppes, P.Y., and Primm, T.P. ( 2005 ) Mycobacterium avium enters a state of metabolic dormancy in response to starvation. Tuberculosis 85: 147 – 158.en_US
dc.identifier.citedreferenceBachman, M.A., and Swanson, M.S. ( 2001 ) RpoS co-operates with other factors to induce Legionella pneumophila virulence in the stationary phase. Mol Microbiol 40: 1201 – 1214.en_US
dc.identifier.citedreferenceBachman, M.A., and Swanson, M.S. ( 2004a ) Genetic evidence that Legionella pneumophila RpoS modulates expression of the transmission phenotype in both the exponential phase and the stationary phase. Infect Immun 72: 2468 – 2476.en_US
dc.identifier.citedreferenceBachman, M.A., and Swanson, M.S. ( 2004b ) The LetE protein enhances expression of multiple LetA/LetS-dependent transmission traits by Legionella pneumophila. Infect Immun 72: 3284 – 3293.en_US
dc.identifier.citedreferenceBattesti, A., and Bouveret, E. ( 2006 ) Acyl carrier protein/SpoT interaction, the switch linking SpoT-dependent stress response to fatty acid metabolism. Mol Microbiol 62: 1048 – 1063.en_US
dc.identifier.citedreferenceBerger, K.H., and Isberg, R.R. ( 1993 ) Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol Microbiol 7: 7 – 19.en_US
dc.identifier.citedreferenceBerger, K.H., Merriam, J.J., and Isberg, R.R. ( 1994 ) Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene. Mol Microbiol 14: 809 – 822.en_US
dc.identifier.citedreferenceBohnhoff, M., Miller, C.P., and Martin, W.R. ( 1964 ) Resistance of mouse's intestinal tract to experimental Salmonella infection. I. Factors which interfere with the initiation of infection by oral inoculation. J Exp Med 120: 805 – 816.en_US
dc.identifier.citedreferenceBoucher, P.E., Menozzi, F.D., and Locht, C. ( 1994 ) The modular architecture of bacterial response regulators: insights into the activation mechanism of the BvgA transactivator of Bordetella pertussis. J Mol Biol 241: 363 – 377.en_US
dc.identifier.citedreferenceBroich, M., Rydzewski, K., McNealy, T.L., Marre, R., and Flieger, A. ( 2006 ) The global regulatory proteins LetA and RpoS control phospholipase A, lysophospholipase A, acyltransferase, and other hydrolytic activities of Legionella pneumophila JR32. J Bacteriol 188: 1218 – 1226.en_US
dc.identifier.citedreferenceBruggemann, H., Hagman, A., Jules, M., Sismeiro, O., Dillies, M.A., Gouyette, C., et al. ( 2006 ) Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila. Cell Microbiol 8: 1228 – 1240.en_US
dc.identifier.citedreferenceButtke, T.M., and Ingram, L.O. ( 1978 ) Inhibition of unsaturated fatty acid synthesis in Escherichia coli by the antibiotic cerulenin. Biochemistry 17: 5282 – 5286.en_US
dc.identifier.citedreferenceByrne, B., and Swanson, M.S. ( 1998 ) Expression of Legionella pneumophila virulence traits in response to growth conditions. Infect Immun 66: 3029 – 3034.en_US
dc.identifier.citedreferenceCashel, M. ( 1969 ) The control of ribonucleic acid synthesis in Escherichia coli. J Biol Chem 244: 3133 – 3141.en_US
dc.identifier.citedreferenceCashel, M. ( 1994 ) Detection of (p)ppGpp accumulation patterns in Escherichia coli mutants. In Adolph, K.W. (ed.). Methods in Molecular Genetics, Vol. 3. Molecular Microbiology Techniques, Part A. New York: Academic Press, pp. 341 – 356.en_US
dc.identifier.citedreferenceCazalet, C., Rusniok, C., Bruggemann, H., Zidane, N., Magnier, A., Ma, L., et al. ( 2004 ) Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat Genet 36: 1165 – 1173.en_US
dc.identifier.citedreferenceChien, M., Morozova, I., Shi, S., Sheng, H., Chen, J., Gomez, S.M., et al. ( 2004 ) The genomic sequence of the accidental pathogen Legionella pneumophila. Science 305: 1966 – 1968.en_US
dc.identifier.citedreferenceCook, G.A., King, M.T., and Veech, R.L. ( 1978 ) Ketogenesis and malonyl coenzyme A content of isolated rat hepatocytes. J Biol Chem 253: 2529 – 2531.en_US
dc.identifier.citedreferenceDalebroux, ZD, Edwards, R.L., and Swanson M.S. ( 2009 ) SpoT governs Legionella pneumophila differentiation in host macrophages. Mol Microbiol 71: 640 – 658.en_US
dc.identifier.citedreferenceDiRusso, C.C., and Nystrom, T. ( 1998 ) The fats of Escherichia coli during infancy and old age: regulation by global regulators, alarmones and lipid intermediates. Mol Microbiol 27: 1 – 8.en_US
dc.identifier.citedreferenceFaulkner, G., and Garduno, R.A. ( 2002 ) Ultrastructural analysis of differentiation in Legionella pneumophila. J Bacteriol 184: 7025 – 7041.en_US
dc.identifier.citedreferenceFernandez-Moreira, E., Helbig, J.H., and Swanson, M.S. ( 2006 ) Membrane vesicles shed by Legionella pneumophila inhibit fusion of phagosomes with lysosomes. Infect Immun 74: 3285 – 3295.en_US
dc.identifier.citedreferenceFettes, P.S., Forsbach-Birk, V., Lynch, D., and Marre, R. ( 2001 ) Overexpression of a Legionella pneumophila homologue of the E. coli regulator csrA affects cell size, flagellation and pigmentation. Int J Med Microbiol 291: 353 – 360.en_US
dc.identifier.citedreferenceFields, B.S., Benson, R.F., and Besser, R.E. ( 2002 ) Legionella and Legionnaires' disease: 25 years of investigation. Clin Microbiol Rev 15: 506 – 526.en_US
dc.identifier.citedreferenceFlieger, A., Gong, S., Faigle, M., Mayer, H.A., Kehrer, U., MuBotter, J., et al. ( 2000 ) Phospholipase A secreted by Legionella pneumophila destroys alveolar surfactant phospholipids. FEMS Microbiol Lett 188: 129 – 133.en_US
dc.identifier.citedreferenceGarduno, R.A., Garduno, E., Hiltz, M., and Hoffman, P.S. ( 2002 ) Intracellular growth of Legionella pneumophila gives rise to a differentiated form dissimilar to stationary-phase forms. Infect Immun 70: 6273 – 6283.en_US
dc.identifier.citedreferenceGong, L., Takayama, K., and Kjelleberg, S. ( 2002 ) Role of spoT -dependent ppGpp accumulation in the survival of light-exposed starved bacteria. Microbiol 148: 559 – 570.en_US
dc.identifier.citedreferenceGrabner, R., and Meerbach, W. ( 1991 ) Phagocytosis of surfactant by alveolar macrophages in vitro. Am J Physiol 261: L472 – L477.en_US
dc.identifier.citedreferenceHammer, B.K., and Swanson, M.S. ( 1999 ) Co-ordination of Legionella pneumophila virulence with entry into stationary phase by ppGpp. Mol Microbiol 33: 721 – 731.en_US
dc.identifier.citedreferenceHammer, B.K., Tateda, E.S., and Swanson, M.S. ( 2002 ) A two-component regulator induces the transmission phenotype of stationary-phase Legionella pneumophila. Mol Microbiol 44: 107 – 118.en_US
dc.identifier.citedreferenceHeath, R.J., and Rock, C.O. ( 1995 ) Regulation of malonyl-CoA metabolism by acyl-acyl carrier protein and β-ketoacyl-acyl carrier protein synthases in Escherichia coli. J Biol Chem 270: 15531 – 15538.en_US
dc.identifier.citedreferenceHeinzen, R.A., Hackstadt, T., and Samuel, J.E. ( 1999 ) Developmental biology of Coxiella burnetii. Trends Microbiol 7: 149 – 154.en_US
dc.identifier.citedreferenceHood, M.A., Guckert, J.B., White, D.C., and Deck, F. ( 1986 ) Effect of nutrient deprivation on lipid, carbohydrate, DNA, RNA, and protein levels in Vibrio cholerae. Appl Environ Microbiol 52: 788 – 793.en_US
dc.identifier.citedreferenceJackowski, S., and Rock, C.O. ( 1983 ) Ratio of active to inactive forms of acyl carrier protein in Escherichia coli. J Biol Chem 258: 15186 – 15191.en_US
dc.identifier.citedreferenceJacobi, S., Schade, R., and Heuner, K. ( 2004 ) Characterization of the alternative sigma factor σ 54 and the transcriptional regulator FleQ of Legionella pneumophila, which are both involved in the regulation cascade of flagellar gene expression. J Bacteriol 186: 2540 – 2547.en_US
dc.identifier.citedreferenceJoshi, A.D., Sturgill-Koszycki, S., and Swanson, M.S. ( 2001 ) Evidence that Dot-dependent and -independent factors isolate the Legionella pneumophila phagosome from the endocytic network in mouse macrophages. Cell Microbiol 3: 99 – 114.en_US
dc.identifier.citedreferenceLawhon, S.D., Maurer, R., Suyemoto, M., and Altier, C. ( 2002 ) Intestinal short-chain fatty acids alter Salmonella typhimurium invasion gene expression and virulence through BarA/SirA. Mol Microbiol 46: 1451 – 1464.en_US
dc.identifier.citedreferenceLynch, D., Fieser, N., Gloggler, K., Forsbach-Birk, V., and Marre, R. ( 2003 ) The response regulator LetA regulates the stationary-phase stress response in Legionella pneumophila and is required for efficient infection of Acanthamoeba castellanii. FEMS Microbiol Lett 219: 241 – 248.en_US
dc.identifier.citedreferenceMcCleary, W.R., Stock, J.B., and Ninfa, A.J. ( 1993 ) Is acetyl phosphate a global signal in Escherichia coli ? J Bacteriol 175: 2793 – 2798.en_US
dc.identifier.citedreferenceMcCune, S.A., and Harris, R.A. ( 1979 ) Mechanism responsible for 5-(tetradecyloxy)-2-furoic acid inhibition of hepatic lipogenesis. J Biol Chem 254: 10095 – 10101.en_US
dc.identifier.citedreferenceMcNealy, T.L., Forsbach-Birk, V., Shi, C., and Marre, R. ( 2005 ) The Hfq homolog in Legionella pneumophila demonstrates regulation by LetA and RpoS and interacts with the global regulator CsrA. J Bacteriol 187: 1527 – 1532.en_US
dc.identifier.citedreferenceMagnuson, K., Jackowski, S., Rock, C.O., and Cronan, J.E., Jr ( 1993 ) Regulation of fatty acid biosynthesis in Escherichia coli. Microbiol Rev 57: 522 – 542.en_US
dc.identifier.citedreferenceMagnusson, L.U., Farewell, A., and Nystrom, T. ( 2005 ) ppGpp: a global regulator in Escherichia coli. Trends Microbiol 13: 236 – 242.en_US
dc.identifier.citedreferenceMolofsky, A.B., and Swanson, M.S. ( 2003 ) Legionella pneumophila CsrA is a pivotal repressor of transmission traits and activator of replication. Mol Microbiol 50: 445 – 461.en_US
dc.identifier.citedreferenceMolofsky, A.B., Shetron-Rama, L.M., and Swanson, M.S. ( 2005 ) Components of the Legionella pneumophila flagellar regulon contribute to multiple virulence traits, including lysosome avoidance and macrophage death. Infect Immun 73: 5720 – 5734.en_US
dc.identifier.citedreferenceMolofsky, A.B., Byrne, B.G., Whitfield, N.N., Madigan, C.A., Fuse, E.T., Tateda, K., and Swanson, M.S. ( 2006 ) Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. J Exp Med 203: 1093 – 1104.en_US
dc.identifier.citedreferenceOmura, S. ( 1976 ) The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev 40: 681 – 697.en_US
dc.identifier.citedreferencePanek, E., Cook, G.A., and Cornell, N.W. ( 1977 ) Inhibition by 5-(tetradecyloxy)-2-furoic acid of fatty acid and cholesterol synthesis in isolated rat hepatocytes. Lipids 12: 814 – 818.en_US
dc.identifier.citedreferencePizer, E.S., Thupari, J., Han, W.F., Pinn, M.L., Chrest, F.J., Frehywot, G.L., et al. ( 2000 ) Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res 60: 213 – 218.en_US
dc.identifier.citedreferencePost-Beittenmiller, D., Jaworski, J.G., and Ohlrogge, J.B. ( 1991 ) In vivo pools of free and acylated acyl carrier proteins in spinach. J Biol Chem 266: 1858 – 1865.en_US
dc.identifier.citedreferencePurevdorj-Gage, B., Costerton, W.J., and Stoodley, P. ( 2005 ) Phenotypic differentiation and seeding dispersal in non-mucoid and mucoid Pseudomonas aeruginosa biofilms. Microbiology 151: 1569 – 1576.en_US
dc.identifier.citedreferenceRen, T., Zamboni, D.S., Roy, C.R., Dietrich, W.F., and Vance, R.E. ( 2006 ) Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog 2: e18.en_US
dc.identifier.citedreferenceRock, C.O., and Cronan, J.E., Jr ( 1981 ) Acyl carrier protein from Escherichia coli. Methods Enzymol 71: 341 – 351.en_US
dc.identifier.citedreferenceRowbotham, T.J. ( 1986 ) Current views on the relationships between amoebae, legionellae and man. Isr J Med Sci 22: 678 – 689.en_US
dc.identifier.citedreferenceSamuel, J.E., Kiss, K., and Varghees, S. ( 2003 ) Molecular pathogenesis of Coxiella burnetii in a genomics era. Ann N Y Acad Sci 990: 653 – 663.en_US
dc.identifier.citedreferenceSauer, J.D., Bachman, M.A., and Swanson, M.S. ( 2005 ) The phagosomal transporter A couples threonine acquisition to differentiation and replication of Legionella pneumophila in macrophages. Proc Natl Acad Sci USA 102: 9924 – 9929.en_US
dc.identifier.citedreferenceSchujman, G.E., Altabe, S., and de Mendoza, D. ( 2008 ) A malonyl-CoA-dependent switch in the bacterial response to a dysfunction of lipid metabolism. Mol Microbiol 68: 987 – 996.en_US
dc.identifier.citedreferenceSegal, G., Feldman, M., and Zusman, T. ( 2005 ) The Icm/Dot type-IV secretion systems of Legionella pneumophila and Coxiella burnetii. FEMS Microbiol Rev 29: 65 – 81.en_US
dc.identifier.citedreferenceSeyfzadeh, M., Keener, J., and Nomura, M. ( 1993 ) spoT-dependent accumulation of guanosine tetraphosphate in response to fatty acid starvation in Escherichia coli. Proc Natl Acad Sci USA 90: 11004 – 11008.en_US
dc.identifier.citedreferenceShi, C., Forsbach-Birk, V., Marre, R., and McNealy, T.L. ( 2006 ) The Legionella pneumophila global regulatory protein LetA affects DotA and Mip. Int J Med Microbiol 296: 15 – 24.en_US
dc.identifier.citedreferenceSrivatsan, A., and Wang, J.D. ( 2008 ) Control of bacterial transcription, translation and replication by (p)ppGpp. Curr Opin Microbiol 11: 100 – 105.en_US
dc.identifier.citedreferenceStone, B.J., and Abu Kwaik, Y. ( 1999 ) Natural competence for DNA transformation by Legionella pneumophila and its association with expression of type IV pili. J Bacteriol 181: 1395 – 1402.en_US
dc.identifier.citedreferenceSturgill-Koszycki, S., and Swanson, M.S. ( 2000 ) Legionella pneumophila replication vacuoles mature into acidic, endocytic organelles. J Exp Med 192: 1261 – 1272.en_US
dc.identifier.citedreferenceSwanson, M.S., and Isberg, R.R. ( 1995 ) Association of Legionella pneumophila with the macrophage endoplasmic reticulum. Infect Immun 63: 3609 – 3620.en_US
dc.identifier.citedreferenceUlrich, A.K., de Mendoza, D., Garwin, J.L., and Cronan, J.E., Jr ( 1983 ) Genetic and biochemical analyses of Escherichia coli mutants altered in the temperature-dependent regulation of membrane lipid composition. J Bacteriol 154: 221 – 230.en_US
dc.identifier.citedreferenceVance, D., Goldberg, I., Mitsuhashi, I., Bloch, K., Omura, S., and Nomura, S. ( 1972 ) Inhibition of fatty acid synthetases by the antibiotic cerulenin. Biochem Biophys Res Commun 48: 649 – 656.en_US
dc.identifier.citedreferenceVinzing, M., Eitel, J., Lippmann, J., Hocke, A.C., Zahlten, J., Slevogt, H., et al. ( 2008 ) NAIP and Ipaf control Legionella pneumophila replication in human cells. J Immunol 180: 6808 – 6815.en_US
dc.identifier.citedreferenceWarren, W.J., and Miller, R.D. ( 1979 ) Growth of Legionnaires disease bacterium ( Legionella pneumophila ) in chemically defined medium. J Clin Microbiol 10: 50 – 55.en_US
dc.identifier.citedreferenceWatarai, M., Derre, I., Kirby, J., Growney, J.D., Dietrich, W.F., and Isberg, R.R. ( 2001 ) Legionella pneumophila is internalized by a macropinocytotic uptake pathway controlled by the Dot/Icm system and the mouse Lgn1 locus. J Exp Med 194: 1081 – 1096.en_US
dc.identifier.citedreferenceWieland, H., Faigle, M., Lang, F., Northoff, H., and Neumeister, B. ( 2002 ) Regulation of the Legionella mip -promotor during infection of human monocytes. FEMS Microbiol Lett 212: 127 – 132.en_US
dc.identifier.citedreferenceWieland, H., Ullrich, S., Lang, F., and Neumeister, B. ( 2005 ) Intracellular multiplication of Legionella pneumophila depends on host cell amino acid transporter SLC1A5. Mol Microbiol 55: 1528 – 1537.en_US
dc.identifier.citedreferenceWolfe, A.J. ( 2005 ) The acetate switch. Micro Mol Biol Rev 69: 12 – 50.en_US
dc.identifier.citedreferenceZhou, W., Simpson, P.J., McFadden, J.M., Townsend, C.A., Medghalchi, S.M., Vadlamudi, A., et al. ( 2003 ) Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Cancer Res 63: 7330 – 7337.en_US
dc.identifier.citedreferenceZusman, T., Gal-Mor, O., and Segal, G. ( 2002 ) Characterization of a Legionella pneumophila relA insertion mutant and toles of RelA and RpoS in virulence gene expression. J Bacteriol 184: 67 – 75.en_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


Files in this item

Name:
j.1365-2958.2008.06593.x.pdf
Size:
501.5KB
Format:
PDF
View/Open

Show simple item record

Remediation of Harmful Language

The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.

Accessibility

If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.