Targeting of host organelles by pathogenic bacteria: A sophisticated subversion strategy

Nature Reviews Microbiology

Volumn 14, Issue 1, 2015, Pages 5-19

  Escoll, Pedro ^a   Mondino, Sonia ^a   Rolando, Monica ^a   Buchrieser, Carmen ^a  

^a CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL PROTEIN; VIRULENCE FACTOR;

AGROBACTERIUM TUMEFACIENS; ANAPLASMA PHAGOCYTOPHILUM; APOPTOSIS; BACTERIAL INFECTION; BACTERIAL VIRULENCE; BRUCELLA; CELL ORGANELLE; CHLAMYDIA TRACHOMATIS; CHROMATIN STRUCTURE; ENDOPLASMIC RETICULUM; ESCHERICHIA COLI; EUKARYOTIC CELL; GOLGI COMPLEX; HISTONE MODIFICATION; HOST CELL; HOST PATHOGEN INTERACTION; HOST RESISTANCE; HUMAN; LEGIONELLA PNEUMOPHILA; LISTERIA MONOCYTOGENES; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW; SALMONELLA; SALMONELLA ENTERICA; SHIGELLA FLEXNERI; TARGET CELL; TRANSCRIPTION INITIATION; VIBRIO CHOLERAE; ANIMAL; BACTERIUM; BIOLOGICAL MODEL; GROWTH, DEVELOPMENT AND AGING; MICROBIOLOGY; PLANT;

ANIMALS; BACTERIA; EUKARYOTIC CELLS; HOST-PATHOGEN INTERACTIONS; HUMANS; MODELS, BIOLOGICAL; ORGANELLES; PLANTS;

EID: 84951570295     PISSN: 17401526     EISSN: 17401534     Source Type: Journal    
DOI: 10.1038/nrmicro.2015.1     Document Type: Review

References (158)

1. Mills, E., Baruch, K., Aviv, G., Nitzan, M. & Rosenshine, I. Dynamics of the type III secretion system activity of enteropathogenic Escherichia coli. mBio 4, e00303-13 (2013).
2. Mills, E., Baruch, K., Charpentier, X., Kobi, S. & Rosenshine, I. Real-time analysis of effector translocation by the type III secretion system of enteropathogenic Escherichia coli. Cell Host Microbe 3, 104-113 (2008).
3. Nora, T., Lomma, M., Gomez-Valero, L. & Buchrieser, C. Molecular mimicry: an important virulence strategy employed by Legionella pneumophila to subvert host functions. Future Microbiol. 4, 691-701 (2009).
4. Rolando, M. & Buchrieser, C. Post-translational modifications of host proteins by Legionella pneumophila: a sophisticated survival strategy. Future Microbiol. 7, 369-381 (2012).
5. Stebbins, C. E. & Galan, J. E. Structural mimicry in bacterial virulence. Nature 412, 701-705 (2001).
6. Hubber, A. & Roy, C. R. Modulation of host cell function by Legionella pneumophila type IV effectors. Annu. Rev. Cell Dev. Biol. 26, 261-283 (2010).
7. Isberg, R. R., OConnor, T. J. & Heidtman, M. The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat. Rev. Microbiol. 7, 13-24 (2009).
8. Cazalet, C. et al. Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat. Genet. 36, 1165-1173 (2004). This genome analysis gives intriguing new insights, as it is the first to show the presence of an abundance of eukaryotic-like proteins and proteins containing host-interacting domains in a prokaryotic genome.
9. de Felipe, K. S. et al. Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLoS Pathog. 4, e1000117 (2008).
10. Gomez-Valero, L. & Buchrieser, C. Genome dynamics in Legionella: the basis of versatility and adaptation to intracellular replication. Cold Spring Harb. Perspect. Med. 3, a009993 (2013).
11. de Felipe, K. S. et al. Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J. Bacteriol. 187, 7716-7726 (2005).
12. Gomez Valero, L., Runsiok, C., Cazalet, C. & Buchrieser, C. Comparative and functional genomics of Legionella identified eukaryotic like proteins as key players in host-pathogen interactions. Front. Microbiol. 2, 208 (2011).
13. Michard, C. & Doublet, P. Post-translational modifications are key players of the Legionella pneumophila infection strategy. Front. Microbiol. 6, 87 (2015).
14. Rolando, M., Gomez-Valero, L. & Buchrieser, C. Bacterial remodelling of the host epigenome: functional role and evolution of effectors methylating host histones. Cell Microbiol. 17, 1098-1107 (2015).
15. Zhou, Y. & Zhu, Y. Diversity of bacterial manipulation of the host ubiquitin pathways. Cell. Microbiol. 17, 26-34 (2015).
16. Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41-45 (2000).
17. Huang, H., Sabari, B. R., Garcia, B. A., Allis, C. D. & Zhao, Y. SnapShot: histone modifications. Cell 159, 458-458.e1 (2014).
18. Gardner, K. E., Allis, C. D. & Strahl, B. D. Operating on chromatin, a colorful language where context matters. J. Mol. Biol. 409, 36-46 (2011).
19. Akira, S., Uematsu, S. & Takeuchi, O. Pathogen recognition and innate immunity. Cell 124, 783-801 (2006).
20. Schmeck, B. et al. Intracellular bacteria differentially regulated endothelial cytokine release by MAPKdependent histone modification. J. Immunol. 175, 2843-2850 (2005).
21. Schmeck, B. et al. Histone acetylation and flagellin are essential for Legionella pneumophila-induced cytokine expression. J. Immunol. 181, 940-947 (2008).
22. Slevogt, H. et al. Moraxella catarrhalis induces inflammatory response of bronchial epithelial cells via MAPK and NF-κB activation and histone deacetylase activity reduction. Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L818-L826 (2006).
23. Wang, Y., Curry, H. M., Zwilling, B. S. & Lafuse, W. P. Mycobacteria inhibition of IFN-γ induced HLA-DR gene expression by up-regulating histone deacetylation at the promoter region in human THP-1 monocytic cells. J. Immunol. 174, 5687-5694 (2005).
24. Garcia-Garcia, J. C., Barat, N. C., Trembley, S. J. & Dumler, J. S. Epigenetic silencing of host cell defense genes enhances intracellular survival of the rickettsial pathogen Anaplasma phagocytophilum. PLoS Pathog. 5, e1000488 (2009). This study provides the first evidence that a bacterial pathogen translocates proteins to the nucleus.
25. Baxt, L. A., Garza-Mayers, A. C. & Goldberg, M. B. Bacterial subversion of host innate immune pathways. Science 340, 697-701 (2013).
26. Cossart, P. & Lebreton, A. A trip in the New Microbiology with the bacterial pathogen Listeria monocytogenes. FEBS Lett. 588, 2437-2445 (2014).
27. Canonne, J. & Rivas, S. Bacterial effectors target the plant cell nucleus to subvert host transcription. Plant Signal. Behav. 7, 217-221 (2012).
28. Howard, E. A., Zupan, J. R., Citovsky, V. & Zambryski, P. C. The VirD2 protein of A. tumefaciens contains a C-terminal bipartite nuclear localization signal: implications for nuclear uptake of DNA in plant cells. Cell 68, 109-118 (1992). This paper describes VirD2 of A. tumefaciens, which is the first bacterial effector shown to target organelles of eukaryotic cells.
29. Citovsky, V. et al. Biological systems of the host cell involved in Agrobacterium infection. Cell. Microbiol. 9, 9-20 (2007).
30. Cossart, P. Illuminating the landscape of host- pathogen interactions with the bacterium Listeria monocytogenes. Proc. Natl Acad. Sci. USA 108, 19484-19491 (2011).
31. Lebreton, A. et al. A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. Science 331, 1319-1321 (2011).
32. Eskandarian, H. A. et al. A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science 341, 1238858 (2013). Together with reference 31, this report shows that L. monocytogenes modulates the chromatin landscape of its host by recruiting nuclear proteins such as BAHD1 and SIRT2.
33. Ogawa, M., Handa, Y., Ashida, H., Suzuki, M. & Sasakawa, C. The versatility of Shigella effectors. Nat. Rev. Microbiol. 6, 11-16 (2008).
34. Li, H. et al. The phosphothreonine lyase activity of a bacterial type III effector family. Science 315, 1000-1003 (2007).
35. Arbibe, L. et al. An injected bacterial effector targets chromatin access for transcription factor NF-κB to alter transcription of host genes involved in immune responses. Nat. Immunol. 8, 47-56 (2007).
36. Harouz, H. et al. Shigella flexneri targets the HP1-γ subcode through the phosphothreonine lyase OspF. EMBO J. 33, 2606-2622 (2014).
37. Jayamani, E. & Mylonakis, E. Effector triggered manipulation of host immune response elicited by different pathotypes of Escherichia coli. Virulence 5, 733-739 (2014).
38. Shames, S. R. et al. The pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300. Cell. Microbiol. 13, 1542-1557 (2011).
39. Chen, L., Fischle, W., Verdin, E. & Greene, W. C. Duration of nuclear NF-κB action regulated by reversible acetylation. Science 293, 1653-1657 (2001).
40. Pearson, J. S., Riedmaier, P., Marches, O., Frankel, G. & Hartland, E. L. A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-κB for degradation. Mol. Microbiol. 80, 219-230 (2011).
41. Yen, H. et al. NleC, a type III secretion protease, compromises NF-κB activation by targeting p65/RelA. PLoS Pathog. 6, e1001231 (2010).
42. Dillon, S. C., Zhang, X., Trievel, R. C, & Cheng, X. The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol. 6, 227 (2005).
43. Dautry-Varsat, A., Balana, M. E. & Wyplosz, B. Chlamydia-host cell interactions: recent advances on bacterial entry and intracellular development. Traffic 5, 561-570 (2004).
44. Stephens, R. S. et al. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754-759 (1998).
45. Pennini, M. E., Perrinet, S., Dautry-Varsat, A. & Subtil, A. Histone methylation by NUE, a novel nuclear effector of the intracellular pathogen Chlamydia trachomatis. PLoS Pathog. 6, e1000995 (2010).
46. Rolando, M., Rusniok, C., Margueron, R. & Buchrieser, C. [Host epigenetic targeting by Legionella pneumophila]. Med. Sci. (Paris) 29, 843-845 (in French) (2013).
47. Cheung, W. L., Briggs, S. D. & Allis, C. D. Acetylation and chromosomal functions. Curr. Opin. Cell Biol. 12, 326-333 (2000).
48. Li, T. et al. SET-domain bacterial effectors target heterochromatin protein 1 to activate host rDNA transcription. EMBO Rep. 14, 733-740 (2013).
49. Rolando, M. & Buchrieser, C. Legionella pneumophila type IV effectors hijack the transcription and translation machinery of the host cell. Trends Cell Biol. 24, 771-778 (2014).
50. Abrami, L., Reig, N. & van der Goot, F. G. Anthrax toxin: the long and winding road that leads to the kill. Trends Microbiol. 13, 72-78 (2005).
51. Mujtaba, S. et al. Anthrax SET protein: a potential virulence determinant that epigenetically represses NF-κB activation in infected macrophages. J. Biol. Chem. 288, 23458-23472 (2013).
52. Caturegli, P. et al. ankA: an Ehrlichia phagocytophila group gene encoding a cytoplasmic protein antigen with ankyrin repeats. Infect. Immun. 68, 5277-5283 (2000).
53. Pan, X., Luhrmann, A., Satoh, A., Laskowski- Arce, M. A. & Roy, C. R. Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science 320, 1651-1654 (2008).
54. Lee, M. C., Miller, E. A., Goldberg, J., Orci, L. & Schekman, R. Bi-directional protein transport between the ER and Golgi. Annu. Rev. Cell Dev. Biol. 20, 87-123 (2004).
55. Mizuno-Yamasaki, E., Rivera-Molina, F. & Novick, P. GTPase networks in membrane traffic. Annu. Rev. Biochem. 81, 637-659 (2012).
56. Stenmark, H. Rab GTPases as coordinators of vesicle traffic. Nat. Rev. Mol. Cell Biol. 10, 513-525 (2009).
57. Cottam, N. P. & Ungar, D. Retrograde vesicle transport in the Golgi. Protoplasma 249, 943-955 (2012).
58. Behnia, R. & Munro, S. Organelle identity and the signposts for membrane traffic. Nature 438, 597-604 (2005).
59. Jean, S. & Kiger, A. A. Coordination between RAB GTPase and phosphoinositide regulation and functions. Nat. Rev. Mol. Cell Biol. 13, 463-470 (2012).
60. Asrat, S., de Jesus, D. A., Hempstead, A. D., Ramabhadran, V. & Isberg, R. R. Bacterial pathogen manipulation of host membrane trafficking. Annu. Rev. Cell Dev. Biol. 30, 79-109 (2014).
61. Hilbi, H. & Haas, A. Secretive bacterial pathogens and the secretory pathway. Traffic 13, 1187-1197 (2012).
62. Haneburger, I. & Hilbi, H. Phosphoinositide lipids and the Legionella pathogen vacuole. Curr. Top. Microbiol. Immunol. 376, 155-173 (2013).
63. Weber, S. S., Ragaz, C. & Hilbi, H. The inositol polyphosphate 5-phosphatase OCRL1 restricts intracellular growth of Legionella, localizes to the replicative vacuole and binds to the bacterial effector LpnE. Cell. Microbiol. 11, 442-460 (2009).
64. Neunuebel, M. R. & Machner, M. P. The taming of a Rab GTPase by Legionella pneumophila. Small GTPases 3, 28-33 (2012).
65. Sherwood, R. K. & Roy, C. R. A. Rab-centric perspective of bacterial pathogen-occupied vacuoles. Cell Host Microbe 14, 256-268 (2013).
66. Machner, M. P. & Isberg, R. R. A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science 318, 974-977 (2007).
67. Murata, T. et al. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat. Cell Biol. 8, 971-977 (2006). Together with reference 66, this study demonstrates that L. pneumophila translocates a T4SS effector into host cells, and that this effector acts as a RAB1GEF, allowing the activation and recruitment of RAB1 to the LCV.
68. Muller, M. P. et al. The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b. Science 329, 946-949 (2010).
69. Mukherjee, S. et al. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature 477, 103-106 (2011).
70. Neunuebel, M. R. et al. De-AMPylation of the Small GTPase Rab1 by the pathogen Legionella pneumophila. Science 333, 453-456 (2011).
71. Tan, Y., Arnold, R. J. & Luo, Z. Q. Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination. Proc. Natl Acad. Sci. USA 108, 21212-21217 (2011). This article and reference 70 show for the first time that a bacterial pathogen encodes effector proteins that are able to phosphocholinate and dephosphocholinate host proteins.
72. Tan, Y. & Luo, Z. Q. Legionella pneumophila SidD is a deAMPylase that modifies Rab1. Nature 475, 506-509 (2011).
73. Ingmundson, A., Delprato, A., Lambright, D. G. & Roy, C. R. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 450, 365-369 (2007).
74. Mihai Gazdag, E. et al. Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB. EMBO Rep. 14, 199-205 (2013).
75. Schoebel, S., Cichy, A. L., Goody, R. S. & Itzen, A. Protein LidA from Legionella is a Rab GTPase supereffector. Proc. Natl Acad. Sci. USA 108, 17945-17950 (2011).
76. Arasaki, K., Toomre, D. K. & Roy, C. R. The Legionella pneumophila effector DrrA is sufficient to stimulate SNARE-dependent membrane fusion. Cell Host Microbe 11, 46-57 (2012).
77. Liu, Y. & Luo, Z. Q. The Legionella pneumophila effector SidJ is required for efficient recruitment of endoplasmic reticulum proteins to the bacterial phagosome. Infect. Immun. 75, 592-603 (2007).
78. Ragaz, C. et al. The Legionella pneumophila phosphatidylinositol-4 phosphate-binding type IV substrate SidC recruits endoplasmic reticulum vesicles to a replication-permissive vacuole. Cell. Microbiol. 10, 2416-2433 (2008).
79. Creasey, E. A. & Isberg, R. R. The protein SdhA maintains the integrity of the Legionella-containing vacuole. Proc. Natl Acad. Sci. USA 109, 3481-3486 (2012).
80. Horenkamp, F. A. et al. Legionella pneumophila subversion of host vesicular transport by SidC effector proteins. Traffic 15, 488-499 (2014).
81. OConnor, T. J., Boyd, D., Dorer, M. S. & Isberg, R. R. Aggravating genetic interactions allow a solution to redundancy in a bacterial pathogen. Science 338, 1440-1444 (2012).
82. Mousnier, A. et al. A new method to determine in vivo interactomes reveals binding of the Legionella pneumophila effector PieE to multiple Rab GTPases. mBio 5, e01148-14 (2014).
83. Nagai, H., Kagan, J. C., Zhu, X., Kahn, R. A. & Roy, C. R. A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science 295, 679-682 (2002). This is the first study to show that L. pneumophila targets a host cell vesicle-trafficking factor (ARF1) through the action of a T4SS-translocated substrate.
84. Kagan, J. C. & Roy, C. R. Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat. Cell Biol. 4, 945-954 (2002).
85. Folly-Klan, M. et al. A novel membrane sensor controls the localization and ArfGEF activity of bacterial RalF. PLoS Pathog. 9, e1003747 (2013).
86. Finsel, I. et al. The Legionella effector RidL inhibits retrograde trafficking to promote intracellular replication. Cell Host Microbe 14, 38-50 (2013).
87. Boschiroli, M. L. et al. Type IV secretion and Brucella virulence. Vet. Microbiol. 90, 341-348 (2002).
88. Celli, J., Salcedo, S. P. & Gorvel, J. P. Brucella coopts the small GTPase Sar1 for intracellular replication. Proc. Natl Acad. Sci. USA 102, 1673-1678 (2005).
89. de Barsy, M. et al. Identification of a Brucella spp. secreted effector specifically interacting with human small GTPase Rab2. Cell. Microbiol. 13, 1044-1058 (2011).
90. Dohmer, P. H., Valguarnera, E., Czibener, C. & Ugalde, J. E. Identification of a type IV secretion substrate of Brucella abortus that participates in the early stages of intracellular survival. Cell. Microbiol. 16, 396-410 (2014).
91. Myeni, S. et al. Brucella modulates secretory trafficking via multiple type IV secretion effector proteins. PLoS Pathog. 9, e1003556 (2013).
92. Heuer, D. et al. Chlamydia causes fragmentation of the Golgi compartment to ensure reproduction. Nature 457, 731-735 (2009). This work provides evidence that bacteria interact with the Golgi apparatus in epithelial cells and thereby enhance lipid acquisition by and development of the pathogen.
93. Capmany, A. & Damiani, M. T. Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication. PLoS ONE 5, e14084 (2010).
94. Moorhead, A. M., Jung, J. Y., Smirnov, A., Kaufer, S. & Scidmore, M. A. Multiple host proteins that function in phosphatidylinositol-4-phosphate metabolism are recruited to the chlamydial inclusion. Infect. Immun. 78, 1990-2007 (2010).
95. Hackstadt, T., Scidmore-Carlson, M. A., Shaw, E. I. & Fischer, E. R. The Chlamydia trachomatis IncA protein is required for homotypic vesicle fusion. Cell. Microbiol. 1, 119-130 (1999).
96. Delevoye, C. et al. SNARE protein mimicry by an intracellular bacterium. PLoS Pathog. 4, e1000022 (2008).
97. Agaisse, H. & Derre, I. Expression of the effector protein IncD in Chlamydia trachomatis mediates recruitment of the lipid transfer protein CERT and the endoplasmic reticulum-resident protein VAPB to the inclusion membrane. Infect. Immun. 82, 2037-2047 (2014).
98. Elwell, C. A. et al. Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development. PLoS Pathog. 7, e1002198 (2011).
99. Scidmore, M. A. & Hackstadt, T. Mammalian 14-3-3β associates with the Chlamydia trachomatis inclusion membrane via its interaction with IncG. Mol. Microbiol. 39, 1638-1650 (2001).
100. Verbeke, P. et al. Recruitment of BAD by the Chlamydia trachomatis vacuole correlates with hostcell survival. PLoS Pathog. 2, e45 (2006).
101. Cortes, C., Rzomp, K. A., Tvinnereim, A., Scidmore, M. A. & Wizel, B. Chlamydia pneumoniae inclusion membrane protein Cpn0585 interacts with multiple Rab GTPases. Infect. Immun. 75, 5586-5596 (2007).
102. Rzomp, K. A., Moorhead, A. R. & Scidmore, M. A. The GTPase Rab4 interacts with Chlamydia trachomatis inclusion membrane protein CT229. Infect. Immun. 74, 5362-5373 (2006).
103. Moest, T. P. & Meresse, S. Salmonella T3SSs: successful mission of the secret(ion) agents. Curr. Opin. Microbiol. 16, 38-44 (2013).
104. Ramsden, A. E., Holden, D. W. & Mota, L. J. Membrane dynamics and spatial distribution of Salmonella-containing vacuoles. Trends Microbiol. 15, 516-524 (2007).
105. Salcedo, S. P. & Holden, D. W. SseG, a virulence protein that targets Salmonella to the Golgi network. EMBO J. 22, 5003-5014 (2003). This investigation shows that S. Typhimurium interacts with the Golgi network in epithelial cells; it also identifies the effector protein required for the intracellular localization of the bacterium.
106. Abrahams, G. L., Muller, P. & Hensel, M. Functional dissection of SseF, a type III effector protein involved in positioning the Salmonella-containing vacuole. Traffic 7, 950-965 (2006).
107. Deiwick, J. et al. The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche. Infect. Immun. 74, 6965-6972 (2006).
108. Domingues, L., Holden, D. W. & Mota, L. J. The Salmonella effector SteA contributes to the control of membrane dynamics of Salmonella-containing vacuoles. Infect. Immun. 82, 2923-2934 (2014).
109. Kuhle, V., Abrahams, G. L. & Hensel, M. Intracellular Salmonella enterica redirect exocytic transport processes in a Salmonella pathogenicity island 2-dependent manner. Traffic 7, 716-730 (2006).
110. Schroeder, N., Mota, L. J. & Meresse, S. Salmonellainduced tubular networks. Trends Microbiol. 19, 268-277 (2011).
111. Harrison, R. E. et al. Salmonella impairs RILP recruitment to Rab7 during maturation of invasion vacuoles. Mol. Biol. Cell 15, 3146-3154 (2004).
112. Stein, M. A., Leung, K. Y., Zwick, M., Garcia-del Portillo, F. & Finlay, B. B. Identification of a Salmonella virulence gene required for formation of filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Mol. Microbiol. 20, 151-164 (1996).
113. Boucrot, E., Henry, T., Borg, J. P., Gorvel, J. P. & Meresse, S. The intracellular fate of Salmonella depends on the recruitment of kinesin. Science 308, 1174-1178 (2005).
114. Dumont, A. et al. SKIP, the host target of the Salmonella virulence factor SifA, promotes kinesin-1-dependent vacuolar membrane exchanges. Traffic 11, 899-911 (2010).
115. Ohlson, M. B. et al. Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Cell Host Microbe 4, 434-446 (2008).
116. McGourty, K. et al. Salmonella inhibits retrograde trafficking of mannose-6-phosphate receptors and lysosome function. Science 338, 963-967 (2012).
117. McEwan, D. G. et al. PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins. Mol. Cell 57, 39-54 (2015).
118. McEwan, D. G. et al. PLEKHM1 regulates Salmonellacontaining vacuole biogenesis and infection. Cell Host Microbe 17, 58-71 (2015).
119. Mallo, G. V. et al. SopB promotes phosphatidylinositol 3-phosphate formation on Salmonella vacuoles by recruiting Rab5 and Vps34. J. Cell Biol. 182, 741-752 (2008).
120. Braun, V. et al. Sorting nexin 3 (SNX3) is a component of a tubular endosomal network induced by Salmonella and involved in maturation of the Salmonella-containing vacuole. Cell. Microbiol. 12, 1352-1367 (2010).
121. Bujny, M. V. et al. Sorting nexin-1 defines an early phase of Salmonella-containing vacuole-remodeling during Salmonella infection. J. Cell Sci. 121, 2027-2036 (2008).
122. Bakowski, M. A. et al. The phosphoinositide phosphatase SopB manipulates membrane surface charge and trafficking of the Salmonella-containing vacuole. Cell Host Microbe 7, 453-462 (2010).
123. Chan, D. C. Fusion and fission: interlinked processes critical for mitochondrial health. Annu. Rev. Genet. 46, 265-287 (2012).
124. West, A. P., Shadel, G. S. & Ghosh, S. Mitochondria in innate immune responses. Nat. Rev. Immunol. 11, 389-402 (2011). This excellent review summarizes the role of mitochondria during innate immune responses against pathogens.
125. Rudel, T., Kepp, O. & Kozjak-Pavlovic, V. Interactions between bacterial pathogens and mitochondrial cell death pathways. Nat. Rev. Microbiol. 8, 693-705 (2010).
126. Neupert, W. & Herrmann, J. M. Translocation of proteins into mitochondria. Annu. Rev. Biochem. 76, 723-749 (2007).
127. Meyer, D. F. et al. Searching algorithm for type IV secretion system effectors 1.0: a tool for predicting type IV effectors and exploring their genomic context. Nucleic Acids Res. 41, 9218-9229 (2013).
128. Moreno-Altamirano, M. M. et al. Bioinformatic identification of Mycobacterium tuberculosis proteins likely to target host cell mitochondria: virulence factors? Microb. Inform. Exp. 2, 9 (2012).
129. Lucattini, R., Likic, V. A. & Lithgow, T. Bacterial proteins predisposed for targeting to mitochondria. Mol. Biol. Evol. 21, 652-658 (2004).
130. Hicks, S. W. & Galan, J. E. Exploitation of eukaryotic subcellular targeting mechanisms by bacterial effectors. Nat. Rev. Microbiol. 11, 316-326 (2013).
131. Kozjak-Pavlovic, V., Ross, K. & Rudel, T. Import of bacterial pathogenicity factors into mitochondria. Curr. Opin. Microbiol. 11, 9-14 (2008).
132. Mukhopadhyay, A., Ni, L., Yang, C. S. & Weiner, H. Bacterial signal peptide recognizes HeLa cell mitochondrial import receptors and functions as a mitochondrial leader sequence. Cell. Mol. Life Sci. 62, 1890-1899 (2005).
133. Kenny, B. & Jepson, M. Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria. Cell. Microbiol. 2, 579-590 (2000). This study describes the first translocated bacterial effector known to target mitochondria.
134. Papatheodorou, P. et al. The enteropathogenic Escherichia coli (EPEC) Map effector is imported into the mitochondrial matrix by the TOM/Hsp70 system and alters organelle morphology. Cell. Microbiol. 8, 677-689 (2006).
135. Nagai, T., Abe, A. & Sasakawa, C. Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis: critical role of the 16th leucine residue in EspF. J. Biol. Chem. 280, 2998-3011 (2005).
136. Nougayrede, J. P. & Donnenberg, M. S. Enteropathogenic Escherichia coli EspF is targeted to mitochondria and is required to initiate the mitochondrial death pathway. Cell. Microbiol. 6, 1097-1111 (2004).
137. Shifflett, D. E., Clayburgh, D. R., Koutsouris, A., Turner, J. R. & Hecht, G. A. Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo. Lab. Invest. 85, 1308-1324 (2005).
138. Dolezal, P. et al. Legionella pneumophila secretes a mitochondrial carrier protein during infection. PLoS Pathog. 8, e1002459 (2012).
139. Shin, O. S. et al. Type III secretion is essential for the rapidly fatal diarrheal disease caused by non-O1, non-O139 Vibrio cholerae. mBio 2, e00106-11 (2011).
140. Suzuki, M., Danilchanka, O. & Mekalanos, J. J. Vibrio cholerae T3SS effector VopE modulates mitochondrial dynamics and innate immune signaling by targeting Miro GTPases. Cell Host Microbe 16, 581-591 (2014). This important research demonstrates how a bacterial T3SS effector modulates mitochondrial dynamics and affects the host immune response.
141. Niu, H., Kozjak-Pavlovic, V., Rudel, T. & Rikihisa, Y. Anaplasma phagocytophilum Ats-1 is imported into host cell mitochondria and interferes with apoptosis induction. PLoS Pathog. 6, e1000774 (2010).
142. Niu, H., Xiong, Q., Yamamoto, A., Hayashi-Nishino, M. & Rikihisa, Y. Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection. Proc. Natl Acad. Sci. USA 109, 20800-20807 (2012).
143. Huang, J. & Brumell, J. H. Bacteria-autophagy interplay: a battle for survival. Nat. Rev. Microbiol. 12, 101-114 (2014).
144. Khweek, A. A. et al. A bacterial protein promotes the recognition of the Legionella pneumophila vacuole by autophagy. Eur. J. Immunol. 43, 1333-1344 (2013).
145. Choy, A. et al. The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science 338, 1072-1076 (2012).
146. Keyser, P., Elofsson, M., Rosell, S. & Wolf-Watz, H. Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram-negative bacteria. J. Intern. Med. 264, 17-29 (2008).
147. Liu, S. et al. Parkinsons disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet. 8, e1002537 (2012).
148. Goh, Y. L., He, H. & March, J. C. Engineering commensal bacteria for prophylaxis against infection. Curr. Opin. Biotechnol. 23, 924-930 (2012).
149. Rolando, M. et al. Legionella pneumophila effector RomA uniquely modifies host chromatin to repress gene expression and promote intracellular bacterial replication. Cell Host Microbe 13, 395-405 (2013). This study characterizes the first bacterial effector shown to directly modify host chromatin during infection; this modification is due to the histone methyltransferase activity, which is of eukaryotic origin.
150. Costa, T. R. et al. Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat. Rev. Microbiol. 13, 343-359 (2015).
151. Christie, P. J. Type IV secretion: intercellular transfer of macromolecules by systems ancestrally related to conjugation machines. Mol. Microbiol. 40, 294-305 (2001).
152. Hamon, M. A. et al. Histone modifications induced by a family of bacterial toxins. Proc. Natl Acad. Sci. USA 104, 13467-13472 (2007).
153. Stavru, F., Bouillaud, F., Sartori, A., Ricquier, D. & Cossart, P. Listeria monocytogenes transiently alters mitochondrial dynamics during infection. Proc. Natl Acad. Sci. USA 108, 3612-3617 (2011).
154. Dyall, S. D., Brown, M. T. & Johnson, P. J. Ancient invasions: from endosymbionts to organelles. Science 304, 253-257 (2004).
155. Fuchs, Y. & Steller, H. Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat. Rev. Mol. Cell Biol. 16, 329-344 (2015).
156. Reed, J. C. Dysregulation of apoptosis in cancer. J. Clin. Oncol. 17, 2941-2953 (1999).
157. Creagh, E. M. Caspase crosstalk: integration of apoptotic and innate immune signalling pathways. Trends Immunol. 35, 631-640 (2014).
158. Yuan, S. & Akey, C. W. Apoptosome structure, assembly, and procaspase activation. Structure 21, 501-515 (2013).