Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 320 (5883): 1651-1654

Copyright © 2008 by the American Association for the Advancement of Science

Ankyrin Repeat Proteins Comprise a Diverse Family of Bacterial Type IV Effectors

Xiaoxiao Pan,1 Anja Lührmann,1* Ayano Satoh,2* Michelle A. Laskowski-Arce,1{dagger} Craig R. Roy1{ddagger}

Abstract: Specialized secretion systems are used by many bacteria to deliver effector proteins into host cells that can either mimic or disrupt the function of eukaryotic factors. We found that the intracellular pathogens Legionella pneumophila and Coxiella burnetii use a type IV secretion system to deliver into eukaryotic cells a large number of different bacterial proteins containing ankyrin repeat homology domains called Anks. The L. pneumophila AnkX protein prevented microtubule-dependent vesicular transport to interfere with fusion of the L. pneumophila-containing vacuole with late endosomes after infection of macrophages, which demonstrates that Ank proteins have effector functions important for bacterial infection of eukaryotic host cells.

1 Section of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
2 Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.

* These authors contributed equally to this work.

{dagger} Present address: University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, NA5.124, Dallas, TX 75390, USA.

{ddagger} To whom correspondence should be addressed. E-mail: craig.roy{at}

AMPylation Is Critical for Rab1 Localization to Vacuoles Containing Legionella pneumophila.
C. A. Hardiman and C. R. Roy (2014)
mBio 5, e01035-13
   Abstract »    Full Text »    PDF »
Coxiella burnetii effector protein subverts clathrin-mediated vesicular trafficking for pathogen vacuole biogenesis.
C. L. Larson, P. A. Beare, D. Howe, and R. A. Heinzen (2013)
PNAS 110, E4770-E4779
   Abstract »    Full Text »    PDF »
Identification of Coxiella burnetii Type IV Secretion Substrates Required for Intracellular Replication and Coxiella-Containing Vacuole Formation.
M. M. Weber, C. Chen, K. Rowin, K. Mertens, G. Galvan, H. Zhi, C. M. Dealing, V. A. Roman, S. Banga, Y. Tan, et al. (2013)
J. Bacteriol. 195, 3914-3924
   Abstract »    Full Text »    PDF »
Membrane extraction of Rab proteins by GDP dissociation inhibitor characterized using attenuated total reflection infrared spectroscopy.
K. Gavriljuk, A. Itzen, R. S. Goody, K. Gerwert, and C. Kotting (2013)
PNAS 110, 13380-13385
   Abstract »    Full Text »    PDF »
Implication of the VirD4 Coupling Protein of the Lvh Type 4 Secretion System in Virulence Phenotypes of Legionella pneumophila.
P. Bandyopadhyay, E. A. S. Lang, K. S. Rasaputra, and H. M. Steinman (2013)
J. Bacteriol. 195, 3468-3475
   Abstract »    Full Text »    PDF »
Structure of the Legionella effector AnkX reveals the mechanism of phosphocholine transfer by the FIC domain.
V. Campanacci, S. Mukherjee, C. R. Roy, and J. Cherfils (2013)
EMBO J. 32, 1469-1477
   Abstract »    Full Text »    PDF »
Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal.
Z. Lifshitz, D. Burstein, M. Peeri, T. Zusman, K. Schwartz, H. A. Shuman, T. Pupko, and G. Segal (2013)
PNAS 110, E707-E715
   Abstract »    Full Text »    PDF »
Host Pathways Important for Coxiella burnetii Infection Revealed by Genome-Wide RNA Interference Screening.
J. A. McDonough, H. J. Newton, S. Klum, R. Swiss, H. Agaisse, and C. R. Roy (2013)
mBio 4, e00606-12
   Abstract »    Full Text »    PDF »
The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation.
A. Choy, J. Dancourt, B. Mugo, T. J. O'Connor, R. R. Isberg, T. J. Melia, and C. R. Roy (2012)
Science 338, 1072-1076
   Abstract »    Full Text »    PDF »
TolC-Dependent Secretion of an Ankyrin Repeat-Containing Protein of Rickettsia typhi.
S. J. Kaur, M. S. Rahman, N. C. Ammerman, M. Beier-Sexton, S. M. Ceraul, J. J. Gillespie, and A. F. Azad (2012)
J. Bacteriol. 194, 4920-4932
   Abstract »    Full Text »    PDF »
Functional equivalence and evolutionary convergence in complex communities of microbial sponge symbionts.
L. Fan, D. Reynolds, M. Liu, M. Stark, S. Kjelleberg, N. S. Webster, and T. Thomas (2012)
PNAS 109, E1878-E1887
   Abstract »    Full Text »    PDF »
Two Systems for Targeted Gene Deletion in Coxiella burnetii.
P. A. Beare, C. L. Larson, S. D. Gilk, and R. A. Heinzen (2012)
Appl. Envir. Microbiol. 78, 4580-4589
   Abstract »    Full Text »    PDF »
Posttranslational modifications of Rab GTPases help their insertion into membranes.
O. Pylypenko and B. Goud (2012)
PNAS 109, 5555-5556
   Full Text »    PDF »
Reversible phosphocholination of Rab proteins by Legionella pneumophila effector proteins.
P. R. Goody, K. Heller, L. K. Oesterlin, M. P. Muller, A. Itzen, and R. S. Goody (2012)
EMBO J. 31, 1774-1784
   Abstract »    Full Text »    PDF »
Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination.
Y. Tan, R. J. Arnold, and Z.-Q. Luo (2011)
PNAS 108, 21212-21217
   Abstract »    Full Text »    PDF »
The Coxiella burnetii Dot/Icm System Creates a Comfortable Home through Lysosomal Renovation.
H. J. Newton and C. R. Roy (2011)
mBio 2, e00226-11
   Abstract »    Full Text »    PDF »
Dot/Icm Type IVB Secretion System Requirements for Coxiella burnetii Growth in Human Macrophages.
P. A. Beare, S. D. Gilk, C. L. Larson, J. Hill, C. M. Stead, A. Omsland, D. C. Cockrell, D. Howe, D. E. Voth, and R. A. Heinzen (2011)
mBio 2, e00175-11
   Abstract »    Full Text »    PDF »
Mimivirus shows dramatic genome reduction after intraamoebal culture.
M. Boyer, S. Azza, L. Barrassi, T. Klose, A. Campocasso, I. Pagnier, G. Fournous, A. Borg, C. Robert, X. Zhang, et al. (2011)
PNAS 108, 10296-10301
   Abstract »    Full Text »    PDF »
The Coxiella burnetii Cryptic Plasmid Is Enriched in Genes Encoding Type IV Secretion System Substrates.
D. E. Voth, P. A. Beare, D. Howe, U. M. Sharma, G. Samoilis, D. C. Cockrell, A. Omsland, and R. A. Heinzen (2011)
J. Bacteriol. 193, 1493-1503
   Abstract »    Full Text »    PDF »
Interbacterial Macromolecular Transfer by the Campylobacter fetus subsp. venerealis Type IV Secretion System.
S. Kienesberger, C. S. Trummler, A. Fauster, S. Lang, H. Sprenger, G. Gorkiewicz, and E. L. Zechner (2011)
J. Bacteriol. 193, 744-758
   Abstract »    Full Text »    PDF »
Effective--a database of predicted secreted bacterial proteins.
M.-A. Jehl, R. Arnold, and T. Rattei (2011)
Nucleic Acids Res. 39, D591-D595
   Abstract »    Full Text »    PDF »
Large-scale identification and translocation of type IV secretion substrates by Coxiella burnetii.
C. Chen, S. Banga, K. Mertens, M. M. Weber, I. Gorbaslieva, Y. Tan, Z.-Q. Luo, and J. E. Samuel (2010)
PNAS 107, 21755-21760
   Abstract »    Full Text »    PDF »
Legionella pneumophila Strain 130b Possesses a Unique Combination of Type IV Secretion Systems and Novel Dot/Icm Secretion System Effector Proteins.
G. N. Schroeder, N. K. Petty, A. Mousnier, C. R. Harding, A. J. Vogrin, B. Wee, N. K. Fry, T. G. Harrison, H. J. Newton, N. R. Thomson, et al. (2010)
J. Bacteriol. 192, 6001-6016
   Abstract »    Full Text »    PDF »
Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein.
A. Luhrmann, C. V. Nogueira, K. L. Carey, and C. R. Roy (2010)
PNAS 107, 18997-19001
   Abstract »    Full Text »    PDF »
Coxiella burnetii Phase I and II Variants Replicate with Similar Kinetics in Degradative Phagolysosome-Like Compartments of Human Macrophages.
D. Howe, J. G. Shannon, S. Winfree, D. W. Dorward, and R. A. Heinzen (2010)
Infect. Immun. 78, 3465-3474
   Abstract »    Full Text »    PDF »
Functional Characterization of a Phospholipase A2 Homolog from Rickettsia typhi.
M. S. Rahman, N. C. Ammerman, K. T. Sears, S. M. Ceraul, and A. F. Azad (2010)
J. Bacteriol. 192, 3294-3303
   Abstract »    Full Text »    PDF »
Histophilus somni IbpA DR2/Fic in Virulence and Immunoprotection at the Natural Host Alveolar Epithelial Barrier.
B. Zekarias, S. Mattoo, C. Worby, J. Lehmann, R. F. Rosenbusch, and L. B. Corbeil (2010)
Infect. Immun. 78, 1850-1858
   Abstract »    Full Text »    PDF »
Indispensable Role for the Eukaryotic-Like Ankyrin Domains of the Ankyrin B Effector of Legionella pneumophila within Macrophages and Amoebae.
C. T. D. Price, S. Al-Khodor, T. Al-Quadan, and Y. Abu Kwaik (2010)
Infect. Immun. 78, 2079-2088
   Abstract »    Full Text »    PDF »
Genomic, proteomic, and transcriptomic analysis of virulent and avirulent Rickettsia prowazekii reveals its adaptive mutation capabilities.
Y. Bechah, K. El Karkouri, O. Mediannikov, Q. Leroy, N. Pelletier, C. Robert, C. Medigue, J. L. Mege, and D. Raoult (2010)
Genome Res. 20, 655-663
   Abstract »    Full Text »    PDF »
Molecular Pathogenesis of Infections Caused by Legionella pneumophila.
H. J. Newton, D. K. Y. Ang, I. R. van Driel, and E. L. Hartland (2010)
Clin. Microbiol. Rev. 23, 274-298
   Abstract »    Full Text »    PDF »
Molecular Characterization of the Dot/Icm-Translocated AnkH and AnkJ Eukaryotic-Like Effectors of Legionella pneumophila.
F. Habyarimana, C. T. Price, M. Santic, S. Al-Khodor, and Y. A. Kwaik (2010)
Infect. Immun. 78, 1123-1134
   Abstract »    Full Text »    PDF »
The Genome of the Amoeba Symbiont "Candidatus Amoebophilus asiaticus" Reveals Common Mechanisms for Host Cell Interaction among Amoeba-Associated Bacteria.
S. Schmitz-Esser, P. Tischler, R. Arnold, J. Montanaro, M. Wagner, T. Rattei, and M. Horn (2010)
J. Bacteriol. 192, 1045-1057
   Abstract »    Full Text »    PDF »
Biological Diversity of Prokaryotic Type IV Secretion Systems.
C. E. Alvarez-Martinez and P. J. Christie (2009)
Microbiol. Mol. Biol. Rev. 73, 775-808
   Abstract »    Full Text »    PDF »
Conjugation genes are common throughout the genus Rickettsia and are transmitted horizontally.
L. A. Weinert, J. J. Welch, and F. M. Jiggins (2009)
Proc R Soc B 276, 3619-3627
   Abstract »    Full Text »    PDF »
Nuclear Translocated Ehrlichia chaffeensis Ankyrin Protein Interacts with a Specific Adenine-Rich Motif of Host Promoter and Intronic Alu Elements.
B. Zhu, K. A. Nethery, J. A. Kuriakose, A. Wakeel, X. Zhang, and J. W. McBride (2009)
Infect. Immun. 77, 4243-4255
   Abstract »    Full Text »    PDF »
Analysis of the Genome of the Escherichia coli O157:H7 2006 Spinach-Associated Outbreak Isolate Indicates Candidate Genes That May Enhance Virulence.
B. R. Kulasekara, M. Jacobs, Y. Zhou, Z. Wu, E. Sims, C. Saenphimmachak, L. Rohmer, J. M. Ritchie, M. Radey, M. McKevitt, et al. (2009)
Infect. Immun. 77, 3713-3721
   Abstract »    Full Text »    PDF »
The Coxiella burnetii Ankyrin Repeat Domain-Containing Protein Family Is Heterogeneous, with C-Terminal Truncations That Influence Dot/Icm-Mediated Secretion.
D. E. Voth, D. Howe, P. A. Beare, J. P. Vogel, N. Unsworth, J. E. Samuel, and R. A. Heinzen (2009)
J. Bacteriol. 191, 4232-4242
   Abstract »    Full Text »    PDF »
The {alpha}-proteobacteria: the Darwin finches of the bacterial world.
T. J.G. Ettema and S. G.E. Andersson (2009)
Biol Lett 5, 429-432
   Abstract »    Full Text »    PDF »
Silencing of Host Cell CYBB Gene Expression by the Nuclear Effector AnkA of the Intracellular Pathogen Anaplasma phagocytophilum.
J. C. Garcia-Garcia, K. E. Rennoll-Bankert, S. Pelly, A. M. Milstone, and J. S. Dumler (2009)
Infect. Immun. 77, 2385-2391
   Abstract »    Full Text »    PDF »
Bacterial FIC Proteins AMP Up Infection.
C. R. Roy and S. Mukherjee (2009)
Science Signaling 2, pe14
   Abstract »    Full Text »    PDF »
Characterization of a Coxiella burnetii ftsZ Mutant Generated by Himar1 Transposon Mutagenesis.
P. A. Beare, D. Howe, D. C. Cockrell, A. Omsland, B. Hansen, and R. A. Heinzen (2009)
J. Bacteriol. 191, 1369-1381
   Abstract »    Full Text »    PDF »
Comparative Genomics Reveal Extensive Transposon-Mediated Genomic Plasticity and Diversity among Potential Effector Proteins within the Genus Coxiella.
P. A. Beare, N. Unsworth, M. Andoh, D. E. Voth, A. Omsland, S. D. Gilk, K. P. Williams, B. W. Sobral, J. J. Kupko III, S. F. Porcella, et al. (2009)
Infect. Immun. 77, 642-656
   Abstract »    Full Text »    PDF »
Sustained Activation of Akt and Erk1/2 Is Required for Coxiella burnetii Antiapoptotic Activity.
D. E. Voth and R. A. Heinzen (2009)
Infect. Immun. 77, 205-213
   Abstract »    Full Text »    PDF »
Candidate Antigens for Q Fever Serodiagnosis Revealed by Immunoscreening of a Coxiella burnetii Protein Microarray.
P. A. Beare, C. Chen, T. Bouman, J. Pablo, B. Unal, D. C. Cockrell, W. C. Brown, K. D. Barbian, S. F. Porcella, J. E. Samuel, et al. (2008)
Clin. Vaccine Immunol. 15, 1771-1779
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882