Chapter 3 : Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence

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The strategies utilized by intracellular pathogens to propagate their genomes are discussed in this chapter in the context of recent developments in one's understanding of cell biology. The strategies employed by intracellular bacteria, defined by the establishment of replication-permissive niches, include (i) survival and replication within a phagolysosome , (ii) escape from the phagosome and replication within the cytoplasm, (iii) modulation of progression along the endocytic cascade, and (iv) exit from the endocytic cascade by entry into alternative pathways of membrane traffic within the host cell. The study of the cell biology of -containing vacuoles is in its infancy, but it does suggest differences among species. Interestingly, while avoiding interactions with the endocytic cascade, , , and some strains of display intimate interactions with other organelle systems, most notably the endoplasmic reticulum (ER) and mitochondria. The acquisition of the lysosomal marker LAMP, while bypassing the late-endosomal compartment, is explained by the localization of brucellae within vacuoles surrounded by the ER, identified by staining with Sec61β. In summary, the data suggest that -containing phagosomes exit the endocytic pathway and transit through the autophagous pathway en route to their replication-permissive niche, the ER. The study of the mechanisms by which the pathogens infect mammalian cells will undoubtedly yield fascinating insights into both microbiology and cell biology at the most intimate interface between the pathogen and host.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3

Key Concept Ranking

Plasma Membrane
Type III Secretion System
Endoplasmic Reticulum
Golgi Apparatus
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Image of FIGURE 1

Schematic representation of phagosomal maturation and the establishment of the phagolysosomal and cytoplasmic compartments as replication-permissive niches. FP, fluid phase; Lm, . See the text for a detailed description of these and other markers.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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Image of FIGURE 2

Establishment of replication-permissive niches by modulation of the endocytic cascade. PM, plasma membrane; FP, fluid phase. See the text for a detailed description of these and other markers.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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Image of FIGURE 3

Establishment of replication-permissive niches outside the endocytic cascade. PM, plasma membrane; Sm, sphingomyelin. See the text for a detailed description of these and other markers.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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Image of FIGURE 4

Intracellular transport pathways coopted by bacterial pathogens. EE/ReE, early and recycling endosomes; LE, late endosome; PL, phagolysosome; TGN ,-Golgi network. See the text for a discussion.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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1. Abu Kwaik, Y. 1996. The phagosome containing Legionella pneumophila within the protozoan Hartmannella vermiformis is surrounded by the rough endoplasmic reticulum. Appl. Environ. Microbiol. 62:20222028.
2. Abu Kwaik, Y.,, L.-Y. Gao,, B. J. Stone,, C. Venkataraman,, and O. Harb. 1998. Invasion of protozoa by Legionella pneumophila and its role in bacterial ecology and pathogenesis. Appl. Environ. Microbiol. 64:31343139.
3. Akhamova, A.,, F. Voncken,, T. van Alen,, A. van Hoek,, B. Boxma,, G. Vogenls,, M. Veenhuis,, and J. Hackstein. 1998. A hydrogenosome with a genome. Nature 396:527528.
4. Alpuche-Aranda, C. M.,, E. L. Racoosin,, J. A. Swanson,, and S. I. Miller. 1994. Salmonella stimulate macrophage macropinocytosis and persist within spacious phagosomes. J. Exp. Med. 179: 601608.
5. Alpuche-Aranda, C. M.,, J. A. Swanson,, W. P. Loomis,, and S. I. Miller. 1992. Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes. Proc. Natl. Acad. Sci. USA 89:1007910083.
6. Alvarez-Dominguez, C.,, A. M. Barbieri,, W. Beron,, A. Wandinger-Ness,, and P. D. Stahl. 1996. Phagocytosed live Listeria monocytogenes influences Rab 5 regulated in vitro phagosome-endosome fusion. J. Biol. Chem. 271:1383413843.
7. Alvarez-Dominguez, C.,, R. Roberts,, and P. Stahl. 1997. Internalized Listeria monocytogenes modulates intracellular trafficking and delays maturation of the phagosome. J. Cell Sci. 110: 731743.
8. Andersson, S.,, A. Zomorodipour,, J. Andersson,, T. Sicheritz-Ponten,, U. Alsmark,, R. Podowski,, A. Naslund,, A.-S. Eriksson,, H. Winkler,, and C. Kurland. 1998. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396:133140.
9. Andrews, H.,, J. Vogel,, and R. Isberg. 1998. Identification of linked Legionella pneumophila genes essential for intracellular growth and evasion of the endocytic pathway. Infect. Immun. 66: 950958.
10. Andrews, N. W.,, and P. Webster. 1991. Phagolysosomal escape by intracellular pathogens. Parasitol. Today 7:335340.
11. Baca, O.,, Y. Li,, and H. Kumar. 1994. Survival of the Q-fever agent Coxiella burnetii in the phagolysosome. Trends Microbiol. 2:476480.
12. Baca, O.,, and D. Paretsky. 1983. Q-fever and Coxiella burnetii: a model for host-parasite interactions. Microbiol. Rev. 47:127149.
13. Barker, L.,, K. George,, S. Falkow,, and P. Small. 1997. Differential trafficking of live and dead Mycobacterium marinum organisms in macrophages. Infect. Immun. 65:14971502.
14. Barnewall, R.,, Y. Rikihisa,, and E. Lee. 1997. Ehrlichia chaffeensis inclusions are early endosomes which selectively accumulate transferrin receptor. Infect. Immun. 65:14551461.
15. Bavoil, P.,, and R.-C. Hsia. 1998. Type III secretion in Chlamydia: a case for deja vu? Mol. Microbiol 28:860862.
16. Bavoil, P.,, O. Ohlin,, and J. Schachter. 1984. Role of disulfide bonding in outer membrane structure and permeability of Chlamydia trachomatis. Infect. Immun. 44:479485.
17. Belden, W.,, and S. Miller. 1994. Further characterization o f the PhoP regulon: identification of new PhoP-activated virulence loci. Infect. Immun. 62:50955101.
18. Berger, K. H.,, and R. R. Isberg. 1993. Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol. Microbiol. 7:719.
19. Berger, K. H.,, J. J. Merriam,, and R. R. Isberg. 1994. Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene. Mol. Microbiol. 14: 809822 .
20. Bernardini, M. L.,, J. Mounier,, H. D'Hauteville,, M. Coquis-Rondon,, and P. J. Sansonetti. 1989. Identification of icsA, a plasmid locus o f ShigellaJlexneri that governs bacterial intraand intercellular spread through interaction with F-actin. Proc. Natl. Acad. Sci. USA 86:38673871.
21. Beron, W.,, C. Alvarez-Dominguez,, L. Mayorga,, and P. Stahl. 1995. Membrane traffic along the phagocytic pathway. Trends Cell Biol. 5: 100104.
22. Beron, W.,, M. Colombo,, L. Mayorga,, and P. Stahl. 1995. In-vitro reconstitution of phagosome- endosome fusion: evidence for regulation by heterotrimeric GTPases. Arch. Biochem. Biophys. 317:337342.
23. Bielecki, J.,, P. Youngman,, P. Connelly,, and D. A. Portnoy. 1990. Bacillus subtilis expressing a haemolysin gene from Listeria monocytogenes can grow in mammalian cells. Nature 345:175176.
24. Blander, S. J.,, R. F. Breiman,, and M. A. Horwitz. 1989. A live avirulent mutant Legionella vaccine induces protective immunity against lethal aerosol challenge. J. Clin. Investig. 83:810815.
25. Bozue, J. A.,, and W. Johnson. 1996. Interaction of Legionella pneumophila with Acanthamoeba castellani: uptake by coiling phagocytosis and inhibition of phagosome-lysosome fusion. Infect. Immun. 64:668673.
26. Brand, B. C.,, A. B. Sadosky,, and H. Shuman. 1994. The Legionella pneumophila km locus: a set of genes required for intracellular multiplication in human macrophages. Mol. Microbiol. 14: 797808.
27. Buchmeier, N. A.,, and F. Heffron. 1991. Inhibition of macrophage phagosome-lysosome fusion by Salmonella typhimurium. Infect. Immun. 59: 22322238.
28. Bui, E.,, P. Bradley,, and P. Johnson. 1996. A common evolutionary origin for mitochondria and hydrogenosomes. Proc. Natl. Acad. Sci. USA 93:96519656.
29. Chen, Y.,, and A. Zychlinsky. 1994. Apoptosis induced by bacterial pathogens. Microb. Pathog. 17: 203212.
30. Clark, C.,, and A. Roger. 1995. Direct evidence for the secondary loss of mitochondria in Entamoeba histolytica. Proc. Natl. Acad. Sci. USA 92:65186521.
31. Clemens, D.,, and M. Horwitz. 1996. The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accesible to exogenously administered transferrin. J. Exp. Med. 184: 13491355.
32. Clemens, D. L. 1996. Characterization of the Mycobacterium tuberculosis phagosome. Trends Microbiol. 4:113118.
33. Clemens, D. L.,, and M. A. Horwitz. 1995. Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosome maturation is inhibited. J. Exp. Med. 181:257270.
34. Clemens, D. L.,, and M. A. Horwitz. 1996. The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin. J. Exp. Med. 184: 13491355.
35. Cole, S.,, R. Brosch,, J. Parkhill,, T. Gamier,, C. Churcher,, D. Harris,, S. Gordon,, K. Eiglmeier,, S. Gas,, C. I. Barry,, F. Tekaia,, K. Badcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, and B. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537544.
36. Cossart, P.,, P. Boquet,, S. Normark,, and R. Rappuoli. 1996. Cellular microbiology emerging. Science 121:315316.
37. Cossart, P.,, and M. Lecuit. 1998. Interactions of Listeria monocytogenes with mammalian cells during entry and actin based movement: bacteria factors, cellular ligands and signaling. EMBO J. 17: 37973806.
38. DeChastellier, C.,, T. Lang,, and T. Thilo. 1995. Phagocytic processing of the macrophage endoparasite, Mycobacterium avium, in comparison to phagosomes which contain Bacillus subtilis or latex beads. Eur. J. Cell Biol. 68:167182.
39. Desjardins, M.,, J. E. Celis,, G. van Meer,, H. Dieplinger,, A. Jahraus,, G. Griffiths,, and L. A. Huber. 1994. Molecular characterization of phagosomes. J. Biol. Chem. 269:3219432200.
40. Desjardins, M.,, L. Huber,, R. Parton,, and G. Griffiths. 1994. Biogenesis of phagolysosomes proceeds through a sequential series o f interactions with the endocytic apparatus. J. Cell Biol. 124: 677688.
41. Desjardins, M.,, N. Nzala,, R. Corsini,, and C. Rondeau. 1997. Maturation of phagosomes is accompanied by changes in their fusion properties and size selective acquisition of solute materials from endosomes. J. Cell. Sci. 110:23032314.
42. Doborowski, J. M.,, and L. D. Sibley. 1996. Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton. Cell 84:933939.
43. Dunn, W. 1994. Autophagy and related mechanisms of lysosome-mediated protein degradation. Trends Cell Biol. 4:139143.
44. Dunn, W. 1990. Studies on the mechanism of autophagy: formation of the autophagic vacuole. J. Cell. Biol. 110:19231933.
45. Eissenberg, L. G.,, and P. B. Wyrick. 1981. Inhibition o f phagolysosomal fusion is localized to the Chlamydia psittaci-hden vacuoles. Infect. Immun. 32:880896.
46. Eissenberg, L. G.,, P. B. Wyrick,, C. H. Davis,, and J. W. Rumpp. 1983. Chlamydia psittaci elementary body envelopes: ingestion and inhibition of lysosomal fusion. Infect. Immun. 40:741751.
47. Enright, F. 1990. The Pathogenesis and Pathobiology of Brucella Infection in Domestic Animals. CRC Press, Boca Raton, Fla.
48. Falkow, S. 1998. Who speaks for the microbes? Emerg. Infect. Dis. 4:495497.
49. Feng, Y.,, B. Press,, and A. Wandlinder-Ness. 1995. Rab7: an important regulator of late endocytic membrane traffic. J. Cell Biol. 131: 14351452.
50. Fields, B. S., 1993. Interaction of a pathogen and its natural host. In J. M. Barbaree,, R. F. Breiman,, and A. P. Doufour (ed.), Legionella: Current Status and Emerging Perspectives. ASM Press, Washington, D.C.
51. Finlay, B.,, and P. Cossart. 1997. Exploitation of mammalian host cell functions by bacterial pathogens. Science 276:718725.
52. Finlay, B.,, and S. Falkow. 1997. Common themes in microbial pathogenesis revisited. Microbiol. Mol. Biol. Rev. 61:136139.
53. Francis, C. L.,, T. A. Ryan,, B. D. Jones,, S. J. Smith,, and S. Falkow. 1993. Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria. Nature 364:639642.
54. Frehel, C.,, C. de Chastellier,, T. Lang,, and N. Rastogi. 1986. Evidence for inhibition of fusion of lysosomal and prelysosome compartments with phagosomes in macrophages infected with pathogenic Mycobacterium avium. Infect. Immun. 52: 252262.
55. Frenchick, P.,, R. Markham,, and A. Cochrane. 1985. Inhibition of phagosome-lysosome fusion in macrophages by soluble extracts of virulent Brucella abortus. Am. J. Vet. Res. 46:332335.
56. Friis, R. R. 1972. Interactions of L cells and Chlamydia psittaci: entry of the parasite and host responses to its development. J. Bacteriol. 110: 706721.
57. Galan, J. 1996. Molecular genetic basis of Salmonella entry into host cells. Mol. Microbiol. 20: 263271.
58. Garcia-del Portillo, F.,, and B. B. Finlay. 1995. Targeting of Salmonella typhimurium to vesicles containing lysosomal membrane glycoproteins bypasses compartments with mannose 6 phosphate receptors. J. Cell Biol. 129:8197.
59. Garcia-del Portillo, F.,, and B. B. Finlay. 1995. The varied lifestyles of intracellular pathogens within eukaryotic vacuolar compartments. Trends Microbiol. 3:373380.
60. Gordon, A. H.,, P. D. Hart,, and M. R. Young. 1980. Ammonia inhibits phagosome-lysosome fusion in macrophages. Nature 286:7980.
61. Goren, M.,, P. Hart,, M. Young,, and J. Armstrong. 1976. Prevention of phagosome-lysosome fusion in cultured macrophages by sulfatides of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 73:25102514.
62. Grinstein, S.,, A. Nanda,, G. Lukacs,, and O. Rotstein. 1992. V-ATPases in phagocytic cells. J. Exp. Biol. 172:179192.
63. Gupta, R.,, and G. Golding. 1996. The origin of the eukaryotic cell. Trends Biochem. Sci. 21: 166171.
64. Haas, A. 1998. Reprogramming the phagocytic pathway–intracellular pathogens and their vacuoles. Mol. Membr. Biol. 15:103121.
65. Hackstadt, T.,, E. Fischer,, M. Scidmore,, D . Rockey,, and R. Heizen. 1997. Origins and functions of the chlamydial inclusion. Trends Microbiol. 5:288293.
66. Hackstadt, T.,, D. D. Rockey,, R. A. Heizen,, and M. A. Scidmore. 1996. Chlamydia trachomatis interrupts an exocytic pathway to acquire endogenously synthesized sphingomyelin in transit from the Golgi apparatus to the plasma membrane. EMBOJ. 15:964977.
67. Hackstadt, T.,, M. Scidmore,, and D. Rockey. 1995. Lipid metabolism in Chlamydia trachomatisinfected cells: directed trafficking of Golgi-derived sphingolipids to the chlamydial inclusion. Proc. Natl. Acad. Sci. USA 92:48774881.
68. Hale, T. L. 1991. Genetic basis of virulence in Shigella species. Microbiol. Rev. 55:206224.
69. Harding, C.,, R. Song,, J. Griffin,, J. France,, M. Wick,, J. Pfeifer,, and H. Geuze. 1995. Processing of bacterial antigens for presentation to class I and II MHC-restricted T lymphocytes. Infect. Agents Dis. 4:112.
70. Hart, P.,, and M. Young. 1991. Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic Mycobacterium and a nonpathogenic yeast. J. Exp. Med. 174:881889.
71. Hart, P.,, M. Young,, M. Jordan,, W. Perkins,, and M. Geisow. 1983. Chemical inhibitors of phagosome-lysosome fusion in cultured macrophages also inhibit saltatory lysosomal movements. J. Exp. Med. 158:477492.
72. Hart, G.,, D. L. Clemens,, and M. A. Horwitz. 1994. Glutamine synthetase of Mycobacterium tuberculosis: extracellular release and characterization of its enzymatic activity. Proc. Natl. Acad. Sci. USA 91:93429346.
73. Heizen, R. A.,, M. A. Scidmore,, D. D. Rockey,, and T. Hackstadt. 1996. Differential interactions with the endocytic and exocytic pathways distinguish the parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis. Infect. Immun. 64:796809.
74. Homuth, M.,, P. Valentin-Weigand,, M. Rohde,, and G. Gerlach. 1998. Identification and characterization of a novel extracellular ferric reductase from Mycobacterium paratuberculosis. Infect. Immun. 66:710716.
75. Horwitz, M. A. 1987. Characterization of avirulent mutant Legionella pneumophila that survive but do not multiply within human monocytes. J. Exp. Med. 166:13101328.
76. Horwitz, M. A. 1983. Formation of a novel phagosome by the Legionnaires disease bacterium (Legionella pneumophila) in human monocytes. J. Exp. Med. 158:13191331.
77. Horwitz, M. A.,, and F. R. Maxfield. 1984. Legionella pneumophila inhibits acidification of its phagosome in human monocytes. J. Cell Biol. 99:19361943.
78. Horwitz, M. A. 1983. The Legionnaires disease bacterium (Legionella pneumophila) inhibits phagosome- lysosome fusion in human monocytes, f. Exp. Med. 158:21082126.
79. Horwitz, M. A. 1984. Phagocytosis of the Legionnaires disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil. Cell 36:2733.
80. Hsia, R.-C.,, Y. Pannekoek,, E. Ingerowski,, and P. Bavoil. 1997. Type III secretion genes identify a putative virulence locus of Chlamydia. Mol. Microbiol. 25:351359.
81. Hueck, C. 1998. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62:379433.
82. Ishibashi, Y.,, and T. Arai. 1990. Specific inhibition of phagosome-lysosome fusion in murine macrophages mediated by Salmonella typhimurium infection. FEMS Microbiol. Immunol. 64:3555.
83. Jacobs, W. R.,, and B. R. Bloom,. 1994. Molecular genetic strategies for identifying virulence determinants of Mycobacterium tuberculosis. In B. R. Bloom (ed.), Tuberculosis: Pathogenesis, Prevention and Control. ASM Press, Washington, D.C.
84. Jahrus, A.,, B. Storrie,, G. Griffith,, and M. Desjardins. 1994. Evidence for retrograde traffic between terminal lysosomes and the prelysosomal/ late endosomal compartment. J. Cell Sci. 107:145157.
85. Joiner, K. 1997. Membrane-protein traffic in pathogen infected cells. J. Clin. Investig. 99:18141816.
86. Joiner, K. A. 1994. Vacuolar membranes surrounding intracellular pathogens: where do they come from and what do they do? Infect. Agents Dis. 2:215219.
87. Lawn, A. M.,, W. A. Blythe,, and J. Taverne. 1973. Interactions of T R I C agents with macrophages and BHK-21 cells observed by electron microscopy. J. Hyg. 71:515528.
88. Leung, K.,, and B. Finlay. 1991. Intracellular replication is essential for virulence of Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 88: 1147011474.
89. Liou, W.,, H. Geuze,, M. Geelen,, and J. Slot. 1997. The autophagic and endocytic pathways converge at the nascent autophagic vacuoles. J. Cell Biol. 136:6170.
90. Lipsky, N. G.,, and R. E. Pagano. 1985. Intracellular translocation of fluorescent sphingolipids in cultured fibroblasts: endogenously synthesized sphingomyelin and glucocerebroside analogues pass through the Golgi apparatus en route to the plasma membrane. J. Cell. Biol. 100:2734.
91. Maara, A.,, S. Blander,, M. A. Horwitz,, and H. A. Shuman. 1992. Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc. Natl. Acad. Sci. USA 89:96079611.
92. Martin, W.,, and M. Muller. 1998. The hydrogen hypothesis for the first eukaryote. Nature 392: 3741.
93. Matsumoto, A., 1988. Structural characteristics of chlamydial bodies, p. 2145. In A. L. Barron (ed.), Microbiology of Chlamydia. CRC Press, Boca Raton, Fla.
94. Matsumoto, A.,, I. Bessho,, K. Uehira,, and T. Suda. 1991. Morphological studies on the association o f mitochondria with chlamydial inclusions. J. Electron Microsc. 40:356363.
95. Matzanke, B.,, R. Bohnke,, U. Mollmann,, R. Reissbrodt,, V. Schunemann,, and A. Trautwein. 1997. Iron uptake and intracellular metal transfer in mycobacteria mediated by xenosiderophores. Biometals 10:193203.
96. McClarty, G. 1994. Chlamydiae and the biochemistry of intracellular parasitism. Trends Microbiol. 2:157164.
97. McDade, J. E.,, C. C. Shepherd,, D. W. Frase,, T. R. Tsai,, M. A. Redus,, W. R. Dowdle, and the Laboratory Investigation Team. 1977. Legionnaires disease: isolation of a bacterium and demonstration of its role in other respiratory disease. N. Engl.f. Med. 297:11971203.
98. Meresse, S.,, S. Gorvel,, and P. Chavrier. 1995. The rab7 GTPase resides on a vesicular compartment connected to lysosomes. J. Cell Sci. 108: 33493358.
99. Miller, S. 1991. PhoP/PhoQ: macrophage-specific modulators of Salmonella virulence? Mol Microbiol. 5:20732078.
100. Mor, N.,, and M. Goren. 1987. Discrepancy in assessment of phagosome-lysosome fusion with two lysosomal markers in murine macrophages infected with Candida albicans. Infect. Immun. 55: 16631667.
101. Moulder, J. W. 1985. Comparative biology of intracellular parasitism. Microbiol. Rev. 49: 298337.
102. Moulder, J. W. 1991. Interactions of chlamydiae with host cells in vitro. Microbiol. Rev. 55: 143190.
103. Muller, M. 1993. The hydrogenosome.J. Gen. Microbiol 139:28792889.
104. Oh, Y. K.,, C. Alpuche-Aranda,, E. Berthiaume,, T. Jinks,, S. I. Miller,, and J. R. Swanson. 1996. Rapid and complete fusion of macrophage lysosomes with phagosomes containing Salmonella typhimurium. Infect. Immun. 64: 38773883.
105. Oh, Y. K.,, and J. A. Swanson. 1996. Different fates o f phagocytosed particles after delivery into macrophage lysosomes. J. Cell Biol 132: 585593.
106. Olkonnen, V.,, and H. Stenmark. 1997. The role of Rab GTPases in membrane traffic. Int. Rev. Cytol 176:185.
107. Paulnock, D. 1994. The molecular biology of macrophage activation. Immunol Ser. 60:4762.
108. Pfeffer, S. 1996. Transport vesicle docking: SNAREs and associates. Annu. Rev. Cell Dev. Biol 12:441461.
109. Pinder, J.,, R. Fowler,, A. Dluezewski,, L. Bannister,, F. Lavin,, G. Mitchell,, R. Wilson,, and W. Gratzer. 1998. Actomyosin motor in the merozoite of the malaria parasite Plasmodium falciparum: implications for red cell invasion. J. Cell Sci. 111:18311839.
110. Pitt, A.,, L. Mayorga,, P. Stahl,, and A. Schwartz. 1992. Alterations in the protein composition of maturing phagosomes. J. Clin. Investig. 90:19781983.
111. Pitt, A.,, L. S. Mayorga,, A. L. Schwartz,, and P. D. Stahl. 1992. Transport of phagosomal components to an endosomal compartment. J. Biol Chem. 267:126132.
112. Pizarro-Cerda, J.,, S. Meresse,, R. G. Parton,, G. van der Goot,, A. Sola-Landa,, I. Lopez-Goni,, E. Moreno,, and J.-P. Gorvel. 1998. Brucella abortus transits through the autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect. Immun. 66:57115724.
113. Pizarro-Cerda, J.,, E. Moreno,, V. Sanguedolce,, J.-L. Mege,, and J.-P. Gorvel. 1998. Virulent Brucella abortus prevents lysosome fusion and is distributed within autophagosomelike compartments. Infect. Immun. 66:23872392.
114. Prain, C. J.,, and J. H. Pearce. 1989. Ultrastructural studies on the intracellular fate of Chlamydia psittaci (strain GPIC) and Chlamydia trachomatis (strain lymphogranuloma venereum 434): modulation o f intracellular events and relationship with the endocytic mechanism. J. Gen. Microbiol 135:21072123.
115. Purcell, M.,, and H. Shuman. 1998. The Legionella pneumophila icmGCDJBF genes are required for killing human macrophages. Infect. Immun. 66:22452255.
116. Rabinovitch, M.,, and P. S. T. Veras. 1996. Cohabitation of Leishmania amazonensis and Coxiella burnetii. Trends Microbiol 4:158161.
117. Ramakrishnan, L.,, and S. Falkow. 1994. Mycobacterium marinum persists in cultured mammalian cells in a temperature-restricted fashion. Infect. Immun. 62:32223229.
118. Ramakrishnan, L.,, R. Valdivia,, J. McKerrow,, and S. Falkow. 1997. Mycobacterium marinum causes both long-term subclinical infection and acute disease in the leopard frog (Rana pipiens). Infect. Immun. 65: 767773.
119. Rathman, M.,, L. Barker,, and S. Falkow. 1997. The unique trafficking pattern of Salmonella typhimurium-containing phagosomes in murine macrophages is independent of the mechanism of bacterial entry. Infect. Immun. 65: 14751485.
120. Rathman, M.,, M. D. Sjaastad,, and S. Falkow. 1996. Acidification of phagosomes containing Salmonella typhimurium in murine macrophages. Infect. Immun. 64:27652773.
121. Rikihisa, Y. 1991. The tribe Ehrlichieae and ehrlichial disease. Clin. Microbiol. Rev. 4:286308.
122. Ristoph, J. D.,, K. W. Hedlund,, and S. Gowda. 1981. Chemically defined medium for Legionella pneumophila growth. J. Clin. Microbiol 13:115119.
123. Rittig, M. G.,, T. Haupl,, and G. R. Burmester. 1994. Coiling phagocytosis: a way for M HC class I presentation ofbacterial antigens? Int. Arch. Allergy Immunol 103:410.
124. Rockey, D. D.,, D. Grosenbach,, D. E. Hruby,, M. G. Peacock,, R. A. Heizen,, and T. Hackstadt. 1996. Chlamydia psittaci IncA is phosphorylated by the host cell and is exposed on the cytoplasmic face of the developing inclusion. Mol Microbiol. 24:2128.
125. Rockey, D. D.,, R. A. Heizen,, and T. Hackstadt. 1995. Cloning and characterization of a Chlamydia psittaci gene coding for a protein localized in the inclusion membrane of infected cells. Mol Microbiol 15:617626.
126. Rothman, J.,, and F. Wieland. 1996. Protein sorting by transport vesicles. Science 272:227.
127. Rothman, J. E. 1994. Mechanisms of intracellular protein transport. Nature 372:5563.
128. Roy, C.,, K. Berger,, and R. Isberg. 1998. Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes ofbacterial uptake. Mol Microbiol 28:663674.
129. Russell, D. G. 1995. Mycobacterium and Leishmanial stowaways in the endosomal network. Trends Cell Biol 5:125128.
130. Russell, D. G. 1998. What does "inhibition of phagosome-lysosome fusion" really mean? Trends Microbiol 6:212214.
131. Russell, D. G.,, J. Dant,, and S. Sturgill-Koszycki. 1996. Mycobacterium avium- and Mycobacterium tuberculosis-containing vacuoles are dynamic, fusion competent vesicles that are accessible to glycosphingolipids from the host cell plasmalemma. J. Immunol 156:47644773.
132. Sadosky, A. B.,, L. A. Wiater,, and H. A. Shuman. 1993. Identification of Legionella pneumophila genes required for growth within and killing o f human macrophages. Infect. Immun. 61: 53615373.
133. Schachter, J. 1988. The intracellular life of Chlamydia. Curr. Top. Microbiol 138:109139.
134. Schachter, J., 1988. Overview of human disease, p. 153165. In A. L. Barron (ed.), Microbiology of Chlamydia. CRC Press, Boca Raton, Fla.
135. Schaible, U.,, S. Sturgill-Koszycki,, P. Schlesinger,, and D. Russell. 1998. The mycobactericidal activity of activated macrophages is concomitant with distinct alterations in the Mycobacterium avium containing phagosome. J. Immunol 160:12901296.
136. Schramm, N.,, C. R. Bagnell,, and P. B. Wyrick. 1996. Vesicles containing Chlamydia trachomatis serovar L2 remain above pH 6 within HEC-1B cells. Infect. Immun. 64:12081214.
137. Scidmore, M. A.,, E. R. Fischer,, and T. Hackstadt. 1996. Sphingolipids and glycoproteins are differentially trafficked to the Chlamydia trachomatis inclusion, f. Cell Biol. 134:363374.
138. Scidmore, M. A.,, D. D. Rockey,, E. R. Fischer,, R. A. Heizen,, and T. Hackstadt. 1996. Vesicular interactions o f the Chlamydia trachomatis inclusion are determined by early protein synthesis rather than route of entry. Infect. Immun. 64:53665372.
139. Segal, G.,, M. Purcell,, and H. Shuman. 1998. Host cell killing and bacterial conjugation require overlapping sets of genes within a 22 kb region of the Legionella pneumophila genome. Proc. Natl Acad. Sci. USA 95:16691674.
140. Segal, G.,, and H. Schuman. 1997. Characterization of a new region required for macrophage killing by Legionella pneumophila. Infect. Immun. 65:50575066.
141. Simons, K.,, and E. Ikonen. 1997. Functional rafts in cell membranes. Nature 387:569572.
142. Sinai, A. P.,, and K. A. Joiner. 1997. Safe haven: the cell biology of nonfusogenic pathogen vacuoles. Annu. Rev. Microbiol 51:415462.
142a. Sinai, A. P.,, S. Paul,, M. Rabinovitch,, G. Kaplan,, and K. A. Joiner. Co-infection of fibroblasts with Coxiella burnetii and Toxoplasma gondii: to each their own. Microbes Infect., in press.
143. Sinai, A. P.,, P. Webster,, and K. A. Joiner. 1997. Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane: a high affinity interaction. J. Cell Sci. 110:21172128.
144. Sola-Landa, A.,, J. Pizzaro-Cerda,, M.-J. Grillo,, E. Moreno,, I. Moriyou,, J.-M. Blasco,, J.-P. Gorvel,, and I. Lopez-Goni. 1998. A two component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence. Mol. Microbiol. 29:125138.
145. Sollner, T.,, S. W. Whiteheart,, M. Brunner,, H. Erdjument-Bromage,, S. Geromanos,, P. Tempst,, and J. E. Rothman. 1993. SNAP receptors implicated in vesicle targeting and fusion. Nature 362:318324.
146. Stephens, R.,, S. Kalman,, C. Lammel,, J. Fan,, R. Marathe,, L. Aravind,, W. Mitchell,, L. Olinger,, R. Tatusov,, Q. Zhao,, E. Koonin,, and R. Davis. 1998. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282:754759.
147. Stephens, R. S. 1993. Challenge of Chlamydia research. Infect. Agents Dis. 1:279293.
148. Storrie, B.,, and M. Desjardin. 1996. The biogenesis of lysosomes: is it a kiss and run, continuous fusion and fission process? Bioessays 18: 895903.
149. Sturgill-Koszycki, S.,, U. E. Schaible,, and D. G. Russell. 1996. Mycobacterium-contaimng phagosomes are accessible to early endosomes and reflect a transitional state in normal phagosome biogenesis. EMBO J. 15:69606968.
150. Sturgill-Koszycki, S.,, P. H. Schlesinger,, P. Chakraborty,, P. L. Haddix,, H. L. Collins,, A. K. Fok,, R. D. Allen,, S. L. Gluck,, J. Heuser,, and D. G. Russell. 1994. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton ATPase. Science 263: 678681.
151. Swanson, M. S.,, and R. R. Isberg. 1995. Association of Legionella pneumophila with the macrophage endoplasmic reticulum. Infect. Immun. 63:36093620.
152. Swanson, M. S.,, and R. R. Isberg. 1996. Identification of Legionella pneumophila mutants that have aberrant intracellular fates. Infect. Immun. 64:25852594.
153. Taraska, T.,, D. M. Ward,, R. S. Ajioka,, P. B. Wyrick,, S. R. Davis-Kaplan,, C. H. Davis,, and J. Kaplan. 1996. The late chlamydia inclusion membrane is not derived from the endocytic pathway and is relatively deficient in host proteins. Infect. Immun. 64:37133727.
154. Tardieux, I.,, P. Webster,, J. Ravesloot,, W. Boron,, J. A. Lunn,, J. E. Heuser,, and N. W. Andrews. 1992. Lysosome recruitment and fusion are early events required for trypanosome invasion of mammalian cells. Cell 71: 11171130.
155. Tavare, J.,, W. A. Blythe,, and R. C. Ballard. 1974. Interactions of TRIC agents with macrophages: effects on lysosomal enzymes of the cell. J. Hyg. 72:297309.
156. Tesh, M. J.,, S. A. Morse,, and R. D. Miller. 1983. Intermediary metabolism in Legionella pneumophila: utilization of amino acids and other compounds as energy sources. J. Bacteriol. 154: 11041109.
157. Theriot, J. A. 1995. The cell biology of infection by intracellular bacterial pathogens. Annu. Rev. Cell Dev. Biol. 11:213239.
158. Tilney, L. G.,, and D. A. Portnoy. 1989. Actin filaments and the growth, movement and spread of the intracellular bacterial parasite, Listeria monocytogenes, f. Cell Biol. 109:15971608.
159. Tribby, I. I. E.,, R. R. Friis,, and J. W. Moulder. 1973. Effect of chloramphenicol, rifampin, and nalidixic acid on Chlamydia psittaci grown in L cells. J. Infect. Dis. 127:155163.
160. Valdavia, R.,, and S. Falkow. 1997. Fluorescence-based isolation of bacterial genes expressed within host cells. Science 277:20072011.
161. Valdavia, R.,, A. Hromockyj,, D. Monack,, L. Ramakrishnan,, and S. Falkow. 1996. Application of green fluorescent protein (GFP) in the study of host-pathogen interaction. Gene 173:4752.
162.Veras, P., C. de Chastellier,, M. Moreau,, V. Villiers,, M. Thibon,, D. Mattei,, and M. Rabinovitch. 1994. Fusion between large phagocytic vesicles: targeting of yeast and other particulates to phagolysosomes that shelter the bacterium Coxiella burnetii or the protozoan Leishmania amazonensis in Chinese hamster ovary cells. J. Cell Sci. 107:30653076.
163. Veras, P.,, C. Moulia,, C. Dauguet,, C. Tunis,, M. Thibon,, and M. Rabinovitch. 1995. Entry and survival of Leishmania amazonensis amastigotes within phagolysosome-like vacuoles that shelter Coxiella burnetii in Chinese hamster ovary cells. Infect. Immun. 63:35023506.
164. Via, L.,, D. Deretic,, R. Ulmer,, N. Hibler,, L. Huber,, and V. Deretic. 1997. Arrested mycobacteria phagosome maturation is caused by a block in vesicle fusion between stages controlled by Rab5 and Rab7. f. Biol. Chem. 212:1332613331.
165. Vogel, J.,, H. Andrews,, S. Wong,, and R. Isberg. 1998. Conjugative transfer by the virulence system of Legionella pneumophila. Science 279:873876.
166. Warren, W. J.,, and R. D. Miller. 1979. Growth of Legionnaires disease bacterium (Legionella pneumophila) in chemically defined medium. J. Gen. Microbiol. 10:5055.
167. Webster, P.,, J. W. Ijdo,, L. M. Chicoine,, and E. Fikrig. 1998. The agent of human granulocytic ehrlichiosis resides in an endosomal compartment. J. Clin. Investig. 101:19321941.
168. Wiater, L.,, K. Dunn,, F. Maxfield,, and H. Shuman. 1998. Early events in phagosome establishment are required for intracellular survival of Legionella pneumophila. Infect. Immun. 66: 44504460.
169. Winkler, H. H. 1990. Rickettsia species (as organisms). Annu. Rev. Cell. Biol. 44:131153.
170. Wyrick, P. B.,, and E. A. Brownridge. 1978. Growth of Chlamydia psittaci in macrophages. Infect. Immun. 19:10541060.
171. Zeichner, S. L. 1983. Isolation and characterization o f macrophage phagosomes containing infectious and heat-inactivated Chlamydia psittaci: two phagosomes with different intracellular behaviors. Infect. Immun. 40:956966.
172. Zeichner, S. L. 1982. Isolation and characterization of phagosomes containing Chlamydia psittaci from L cells. Infect. Immun. 38:325342.
173. Zhu, W.,, J. Arceneaux,, M. Beggs,, B. Byers,, K. Eisenach,, and M. Lundrigan. 1998. Exochelin genes in Mycobacterium smegmatis: identification of an ABC transporter and two non-ribosomal peptide synthetase genes. Mol. Microbiol. 29:629639.
174. Zychlinsky, A.,, M. C. Prevost,, and P. Sansonetti. 1992. Shigella flexneri induces apoptosis in infected macrophages. Nature 358:167169.

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