The myriad roles of cyclic AMP in microbial pathogens: From signal to sword

Nature Reviews Microbiology

Volumn 10, Issue 1, 2012, Pages 27-38

  McDonough, Kathleen A ^a,b   Rodriguez, Ana ^c  

^a WADSWORTH CENTER   (United States)

^b STATE UNIVERSITY OF NEW YORK   (United States)

^c NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE CYCLASE; BACTERIAL TOXIN; CHOLERA TOXIN; CYCLIC AMP; VIRULENCE FACTOR;

BACTERIAL INFECTION; BACTERIAL VIRULENCE; BACTERIUM; CANDIDA ALBICANS; CELL INVASION; CRYPTOCOCCUS NEOFORMANS; FUNGAL VIRULENCE; FUNGUS; GENE EXPRESSION; GENETIC REGULATION; HOST CELL; HOST PATHOGEN INTERACTION; HUMAN; IMMUNE RESPONSE; KINETOPLASTIDA; MYCOBACTERIUM TUBERCULOSIS; MYCOSIS; NONHUMAN; PARASITE VIRULENCE; PORPHYROMONAS GINGIVALIS; PRIORITY JOURNAL; PROTOZOAL INFECTION; PROTOZOON; PSEUDOMONAS AERUGINOSA; REVIEW; SECOND MESSENGER; UPREGULATION; VIBRIO CHOLERAE;

ALVEOLATA; BACTERIA; CYCLIC AMP; FUNGI; GENE EXPRESSION REGULATION; METABOLIC NETWORKS AND PATHWAYS; MODELS, BIOLOGICAL; SIGNAL TRANSDUCTION; VIRULENCE FACTORS;

BACTERIA (MICROORGANISMS); FUNGI; MAMMALIA; PROTOZOA;

EID: 83855165675     PISSN: 17401526     EISSN: 17401534     Source Type: Journal    
DOI: 10.1038/nrmicro2688     Document Type: Review

References (132)

1. Baumann, A., Lange, C. & Soppa, J. Transcriptome changes and cAMP oscillations in an archaeal cell cycle. BMC Cell Biol. 8, 21-40 (2007).
2. Beavo, J. A. & Brunton, L. L. Cyclic nucleotide research-still expanding after half a century. Nature Rev. Mol. Cell Biol. 3, 710-718 (2002).
3. Insel, P. A., Zhang, L., Murray, F., Yokouchi, H. & Zambon, A. C. Cyclic AMP is both a pro-apoptotic and anti-apoptotic second messenger. Acta Physiol. (Oxf.) 26 May 2011 (doi:10.1111/j.1748-1716.2011.02273.x).
4. Tojima, T., Hines, J. H., Henley, J. R. & Kamiguchi, H. Second messengers and membrane trafficking direct and organize growth cone steering. Nature Rev. Neurosci. 12, 191-203 (2011).
5. Camilli, A. & Bassler, B. L. Bacterial small-molecule signaling pathways. Science 311, 1113-1116 (2006).
6. Rumbaugh, K. P. Convergence of hormones and autoinducers at the host/pathogen interface. Anal. Bioanal. Chem. 387, 425-435 (2007).
7. Gomelsky, M. cAMP, c-di-GMP, c-di-AMP and now cGMP: bacteria use them all! Mol. Microbiol. 79, 562-565 (2011).
8. Romling, U. Great times for small molecules: c-di-AMP, a second messenger candidate in bacteria and archaea. Sci. Signal. 1, pe39 (2008).
9. Dalebroux, Z. D., Svensson, S. L., Gaynor, E. C. & Swanson, M. S. ppGpp conjures bacterial virulence. Microbiol. Mol. Biol. Rev. 74, 171-199 (2010).
10. Potrykus, K. & Cashel, M. (p)ppGpp: still magical? Annu. Rev. Microbiol. 62, 35-51 (2008).
11. Springett, G. M., Kawasaki, H. & Spriggs, D. R. Non-kinase second-messenger signaling: new pathways with new promise. Bioessays 26, 730-738 (2004).
12. Simeoni, L., Smida, M., Posevitz, V., Schraven, B. & Lindquist, J. A. Right time, right place: the organization of membrane proximal signaling. Semin. Immunol. 17, 35-49 (2005).
13. Tang, W. J., Yan, S. & Drum, C. L. Class III adenylyl cyclases: regulation and underlying mechanisms. Adv. Second Messenger Phosphoprotein Res. 32, 137-151 (1998).
14. Botsford, J. L. & Harman, J. G. Cyclic AMP in prokaryotes. Microbiol. Rev. 56, 100-122 (1992).
15. Kamenetsky, M. et al. Molecular details of cAMP generation in mammalian cells: a tale of two systems. J. Mol. Biol. 362, 623-639 (2006).
16. Altarejos, J. Y. & Montminy, M. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nature Rev. Mol. Cell Biol. 12, 141-151 (2011).
17. Kolb, A., Busby, S., Buc, H., Garges, S. & Adhya, S. Transcriptional regulation by cAMP and its receptor protein. Annu. Rev. Biochem. 62, 749-795 (1993).
18. Kresge, N., Simoni, R. D. & Hill, R. L. Earl W. Sutherland's discovery of cyclic adenine monophosphate and the second messenger system. J. Biol. Chem. 280, e39-e40 (2005).
19. Serezani, C. H., Ballinger, M. N., Aronoff, D. M. & Peters-Golden, M. Cyclic AMP: master regulator of innate immune cell function. Am. J. Respir. Cell. Mol. Biol. 39, 127-132 (2008).
20. Botsford, J. L. Cyclic nucleotides in procaryotes. Microbiol. Rev. 45, 620-642 (1981).
21. Gorke, B. & Stulke, J. Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nature Rev. Microbiol. 6, 613-624 (2008).
22. Masure, H. R., Shattuck, R. L. & Storm, D. R. Mechanisms of bacterial pathogenicity that involve production of calmodulin-sensitive adenylate cyclases. Microbiol. Rev. 51, 60-65 (1987).
23. Zhan, L. et al. The cyclic AMP receptor protein, CRP, is required for both virulence and expression of the minimal CRP regulon in Yersinia pestis biovar microtus. Infect. Immun. 76, 5028-5037 (2008).
24. Petersen, S. & Young, G. M. Essential role for cyclic AMP and its receptor protein in Yersinia enterocolitica virulence. Infect. Immun. 70, 3665-3672 (2002).
25. Rickman, L. et al. A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. Mol. Microbiol. 56, 1274-1286 (2005).
26. Smith, R. S., Wolfgang, M. C. & Lory, S. An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Infect. Immun. 72, 1677-1684 (2004).
27. Curtiss, R. 3rd & Kelly, S. M. Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic. Infect. Immun. 55, 3035-3043 (1987).
28. Bai, G., Knapp, G. S. & McDonough, K. A. Cyclic AMP signalling in mycobacteria: redirecting the conversation with a common currency. Cell. Microbiol. 13, 349-358 (2011).
29. Wang, M. et al. Microbial hijacking of complement-Toll-like receptor crosstalk. Sci. Signal. 3, ra11 (2010).
30. Lee, H. J., Park, S. J., Choi, S. H. & Lee, K. H. Vibrio vulnificus rpoS expression is repressed by direct binding of cAMP-cAMP receptor protein complex to its two promoter regions. J. Biol. Chem. 283, 30438-30450 (2008).
31. Fuentes, J. A., Jofre, M. R., Villagra, N. A. & Mora, G. C. RpoS-and Crp-dependent transcriptional control of Salmonella Typhi taiA and hlyE genes: role of environmental conditions. Res. Microbiol. 160, 800-808 (2009).
32. Hengge-Aronis, R. Signal transduction and regulatory mechanisms involved in control of the σS (RpoS) subunit of RNA polymerase. Microbiol. Mol. Biol. Rev. 66, 373-395 (2002).
33. Fong, J. C. & Yildiz, F. H. Interplay between cyclic AMP-cyclic AMP receptor protein and cyclic di-GMP signaling in Vibrio cholerae biofilm formation. J. Bacteriol. 190, 6646-6659 (2008).
34. Kim, T. J. et al. Direct transcriptional control of the plasminogen activator gene of Yersinia pestis by the cyclic AMP receptor protein. J. Bacteriol. 189, 8890-8900 (2007).
35. Zhan, L. et al. Direct and negative regulation of the sycO ypkA ypoJ operon by cyclic AMP receptor protein (CRP) in Yersinia pestis. BMC Microbiol. 9, 178 (2009).
36. Nielsen, A. T. et al. A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine. PLoS Pathog. 6, e1001102 (2010).
37. Yahr, T. L., Vallis, A. J., Hancock, M. K., Barbieri, J. T. & Frank, D. W. ExoY, an adenylate cyclase secreted by the Pseudomonas aeruginosa type III system. Proc. Natl Acad. Sci. USA 95, 13899-13904 (1998).
38. Engel, J. & Balachandran, P. Role of Pseudomonas aeruginosa type III effectors in disease. Curr. Opin. Microbiol. 12, 61-66 (2009).
39. Wolfgang, M. C., Lee, V. T., Gilmore, M. E. & Lory, S. Coordinate regulation of bacterial virulence genes by a novel adenylate cyclase-dependent signaling pathway. Dev. Cell 4, 253-263 (2003).
40. Lory, S., Wolfgang, M., Lee, V. & Smith, R. The multi-talented bacterial adenylate cyclases. Int. J. Med. Microbiol. 293, 479-482 (2004).
41. Suh, S. J. et al. Effect of vfr mutation on global gene expression and catabolite repression control of Pseudomonas aeruginosa. Microbiology 148, 1561-1569 (2002).
42. West, S. E., Sample, A. K. & Runyen-Janecky, L. J. The vfr gene product, required for Pseudomonas aeruginosa exotoxin A and protease production, belongs to the cyclic AMP receptor protein family. J. Bacteriol. 176, 7532-7542 (1994).
43. Fuchs, E. L. et al. The Pseudomonas aeruginosa Vfr regulator controls global virulence factor expression through cyclic AMP-dependent and-independent mechanisms. J. Bacteriol. 192, 3553-3564 (2010).
44. Fuchs, E. L. et al. In vitro and in vivo characterization of the Pseudomonas aeruginosa cyclic AMP (cAMP) phosphodiesterase CpdA, required for cAMP homeostasis and virulence factor regulation. J. Bacteriol. 192, 2779-2790 (2010).
45. Endoh, T. & Engel, J. N. CbpA: a polarly localized novel cyclic AMP-binding protein in Pseudomonas aeruginosa. J. Bacteriol. 191, 7193-7205 (2009).
46. Skorupski, K. & Taylor, R. K. Cyclic AMP and its receptor protein negatively regulate the coordinate expression of cholera toxin and toxin-coregulated pilus in Vibrio cholerae. Proc. Natl Acad. Sci. USA 94, 265-270 (1997).
47. Liang, W., Pascual-Montano, A., Silva, A. J. & Benitez, J. A. The cyclic AMP receptor protein modulates quorum sensing, motility and multiple genes that affect intestinal colonization in Vibrio cholerae. Microbiology 153, 2964-2975 (2007).
48. Beyhan, S., Bilecen, K., Salama, S. R., Casper-Lindley, C. & Yildiz, F. H. Regulation of rugosity and biofilm formation in Vibrio cholerae: comparison of VpsT and VpsR regulons and epistasis analysis of vpsT, vpsR, and hapR. J. Bacteriol. 189, 388-402 (2007).
49. Hammer, B. K. & Bassler, B. L. Quorum sensing controls biofilm formation in Vibrio cholerae. Mol. Microbiol. 50, 101-104 (2003).
50. Zhu, J. & Mekalanos, J. J. Quorum sensing-dependent biofilms enhance colonization in Vibrio cholerae. Dev. Cell 5, 647-656 (2003).
51. Matson, J. S., Withey, J. H. & DiRita, V. J. Regulatory networks controlling Vibrio cholerae virulence gene expression. Infect. Immun. 75, 5542-5549 (2007).
52. Miller, M. B., Skorupski, K., Lenz, D. H., Taylor, R. K. & Bassler, B. L. Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell 110, 303-314 (2002).
53. Liang, W., Sultan, S. Z., Silva, A. J. & Benitez, J. A. Cyclic AMP post-transcriptionally regulates the biosynthesis of a major bacterial autoinducer to modulate the cell density required to activate quorum sensing. FEBS Lett. 582, 3744-3750 (2008).
54. Zhu, J. et al. Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc. Natl Acad. Sci. USA 99, 3129-3134 (2002).
55. Zahid, M. S. et al. The cyclic AMP (cAMP)-cAMP receptor protein signaling system mediates resistance of Vibrio cholerae O1 strains to multiple environmental bacteriophages. Appl. Environ. Microbiol. 76, 4233-4240 (2010).
56. Li, C. C., Merrell, D. S., Camilli, A. & Kaper, J. B. ToxR interferes with CRP-dependent transcriptional activation of ompT in Vibrio cholerae. Mol. Microbiol. 43, 1577-1589 (2002).
57. Shenoy, A. R. & Visweswariah, S. S. New messages from old messengers: cAMP and mycobacteria. Trends Microbiol. 14, 543-550 (2006).
58. McCue, L. A., McDonough, K. A. & Lawrence, C. E. Functional classification of cNMP-binding proteins and nucleotide cyclases with implications for novel regulatory pathways in Mycobacterium tuberculosis. Genome Res. 10, 204-219 (2000).
59. Shenoy, A. R., Sreenath, N. P., Mahalingam, M. & Visweswariah, S. S. Characterization of phylogenetically distant members of the adenylate cyclase family from mycobacteria: Rv1647 from Mycobacterium tuberculosis and its orthologue ML1399 from M. leprae. Biochem. J. 387, 541-551 (2005).
60. Linder, J. U., Hammer, A. & Schultz, J. E. The effect of HAMP domains on class IIIb adenylyl cyclases from Mycobacterium tuberculosis. Eur. J. Biochem. 271, 2446-2451 (2004).
61. Linder, J. U., Schultz, A. & Schultz, J. E. Adenylyl cyclase Rv1264 from Mycobacterium tuberculosis has an autoinhibitory N-terminal domain. J. Biol. Chem. 277, 15271-15276 (2002).
62. Tews, I. et al. The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme. Science 308, 1020-1023 (2005).
63. Bai, G., Schaak, D. D. & McDonough, K. A. cAMP levels within Mycobacterium tuberculosis and Mycobacterium bovis BCG increase upon infection of macrophages. FEMS Immunol. Med. Microbiol. 55, 68-73 (2009).
64. Padh, H. & Venkitasubramanian, T. A. Adenosine 3′, 5′-monophosphate in Mycobacterium phlei and Mycobacterium tuberculosis H37Ra. Microbios 16, 183-189 (1976).
65. Agarwal, N., Lamichhane, G., Gupta, R., Nolan, S. & Bishai, W. R. Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase. Nature 460, 98-102 (2009).
66. Bai, G., McCue, L. A. & McDonough, K. A. Characterization of Mycobacterium tuberculosis Rv3676 (CRPMt), a cyclic AMP receptor protein-like DNA binding protein. J. Bacteriol. 187, 7795-7804 (2005).
67. Gazdik, M. A., Bai, G., Wu, Y. & McDonough, K. A. Rv1675c (cmr) regulates intramacrophage and cyclic AMP-induced gene expression in Mycobacterium tuberculosis-complex mycobacteria. Mol. Microbiol. 71, 434-448 (2009).
68. Nambi, S., Basu, N. & Visweswariah, S. S. cAMP-regulated protein lysine acetylases in mycobacteria. J. Biol. Chem. 285, 24313-24323 (2010).
69. Ahuja, N., Kumar, P. & Bhatnagar, R. The adenylate cyclase toxins. Crit. Rev. Microbiol. 30, 187-196 (2004).
70. Krueger, K. M. & Barbieri, J. T. The family of bacterial ADP-ribosylating exotoxins. Clin. Microbiol. Rev. 8, 34-47 (1995).
71. Carbonetti, N. H. Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools. Future Microbiol. 5, 455-469 (2010).
72. Carbonetti, N. H., Artamonova, G. V., Andreasen, C. & Bushar, N. Pertussis toxin and adenylate cyclase toxin provide a one-two punch for establishment of Bordetella pertussis infection of the respiratory tract. Infect. Immun. 73, 2698-2703 (2005).
73. Smith, N., Kim, S. K., Reddy, P. T. & Gallagher, D. T. Crystallization of the class IV adenylyl cyclase from Yersinia pestis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62, 200-204 (2006).
74. Kim, C. et al. Antiinflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus. Proc. Natl Acad. Sci. USA 105, 6150-6155 (2008).
75. Yeager, L. A., Chopra, A. K. & Peterson, J. W. Bacillus anthracis edema toxin suppresses human macrophage phagocytosis and cytoskeletal remodeling via the protein kinase A and exchange protein activated by cyclic AMP pathways. Infect. Immun. 77, 2530-2543 (2009).
76. Maldonado-Arocho, F. J., Fulcher, J. A., Lee, B. & Bradley, K. A. Anthrax oedema toxin induces anthrax toxin receptor expression in monocyte-derived cells. Mol. Microbiol. 61, 324-337 (2006).
77. Rossi Paccani, S. et al. The adenylate cyclase toxins of Bacillus anthracis and Bordetella pertussis promote Th2 cell development by shaping T cell antigen receptor signaling. PLoS Pathog. 5, e1000325 (2009).
78. Guo, Q. et al. Protein-protein docking and analysis reveal that two homologous bacterial adenylyl cyclase toxins interact with calmodulin differently. J. Biol. Chem. 283, 23836-23845 (2008).
79. Vojtova, J., Kamanova, J. & Sebo, P. Bordetella adenylate cyclase toxin: a swift saboteur of host defense. Curr. Opin. Microbiol. 9, 69-75 (2006).
80. Young, J. A. & Collier, R. J. Anthrax toxin: receptor binding, internalization, pore formation, and translocation. Annu. Rev. Biochem. 76, 243-265 (2007).
81. Tang, W. J. & Guo, Q. The adenylyl cyclase activity of anthrax edema factor. Mol. Aspects Med. 30, 423-430 (2009).
82. Lowrie, D. B., Aber, V. R. & Jackett, P. S. Phagosome-lysosome fusion and cyclic adenosine 3′:5′-monophosphate in macrophages infected with Mycobacterium microti, Mycobacterium bovis BCG or Mycobacterium lepraemurium. J. Gen. Microbiol. 110, 431-441 (1979).
83. Kozubowski, L., Lee, S. C. & Heitman, J. Signalling pathways in the pathogenesis of Cryptococcus. Cell. Microbiol. 11, 370-380 (2009).
84. Hogan, D. A. & Sundstrom, P. The Ras/cAMP/PKA signaling pathway and virulence in Candida albicans. Future Microbiol. 4, 1263-1270 (2009).
85. Brakhage, A. A. & Liebmann, B. Aspergillus fumigatus conidial pigment and cAMP signal transduction: significance for virulence. Med. Mycol. 43 (Suppl. 1), S75-S82 (2005).
86. Ramanujam, R. & Naqvi, N. I. PdeH, a high-affinity cAMP phosphodiesterase, is a key regulator of asexual and pathogenic differentiation in Magnaporthe oryzae. PLoS Pathog. 6, e1000897 (2010).
87. Hall, R. A. & Muhlschlegel, F. A. A multi-protein complex controls cAMP signalling and filamentation in the fungal pathogen Candida albicans. Mol. Microbiol. 75, 534-537 (2010).
88. Casadevall, A. & Perfect, J. R. Cryptococcus neoformans. (American Society for Microbiology Press, Washington DC,1998).
89. Pukkila-Worley, R. & Alspaugh, J. A. Cyclic AMP signaling in Cryptococcus neoformans. FEMS Yeast Res. 4, 361-367 (2004).
90. Xue, C., Bahn, Y. S., Cox, G. M. & Heitman, J. G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. Mol. Biol. Cell. 17, 667-679 (2006).
91. Maeng, S. et al. Comparative transcriptome analysis reveals novel roles of the Ras and cyclic AMP signaling pathways in environmental stress response and antifungal drug sensitivity in Cryptococcus neoformans. Eukaryot. Cell 9, 360-378 (2010).
92. Hu, G. et al. Transcriptional regulation by protein kinase A in Cryptococcus neoformans. PLoS Pathog. 3, e42 (2007).
93. Pukkila-Worley, R. et al. Transcriptional network of multiple capsule and melanin genes governed by the Cryptococcus neoformans cyclic AMP cascade. Eukaryot. Cell 4, 190-201 (2005).
94. Alspaugh, J. A., Perfect, J. R. & Heitman, J. Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP. Genes Dev. 11, 3206-3217 (1997).
95. D'Souza, C. A. et al. Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol. Cell Biol. 21, 3179-3191 (2001).
96. Granger, D. L., Perfect, J. R. & Durack, D. T. Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide. J. Clin. Invest. 76, 508-516 (1985).
97. Mogensen, E. G. et al. Cryptococcus neoformans senses CO2 through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1. Eukaryot. Cell 5, 103-111 (2006).
98. Klengel, T. et al. Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Curr. Biol. 15, 2021-2026 (2005).
99. Bahn, Y. S., Cox, G. M., Perfect, J. R. & Heitman, J. Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence. Curr. Biol. 15, 2013-2020 (2005).
100. Leroy, O. et al. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006). Crit. Care Med. 37, 1612-1618 (2009).
101. Fang, H. M. & Wang, Y. RA domain-mediated interaction of Cdc35 with Ras1 is essential for increasing cellular cAMP level for Candida albicans hyphal development. Mol. Microbiol. 61, 484-496 (2006).
102. Park, H. et al. Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell. Microbiol. 7, 499-510 (2005).
103. Giacometti, R., Kronberg, F., Biondi, R. M. & Passeron, S. Catalytic isoforms Tpk1 and Tpk2 of Candida albicans PKA have non-redundant roles in stress response and glycogen storage. Yeast 26, 273-285 (2009).
104. Harcus, D., Nantel, A., Marcil, A., Rigby, T. & Whiteway, M. Transcription profiling of cyclic AMP signaling in Candida albicans. Mol. Biol. Cell 15, 4490-4499 (2004).
105. Maidan, M. M. et al. The G protein-coupled receptor Gpr1 and the Gα protein Gpa2 act through the cAMP-protein kinase A pathway to induce morphogenesis in Candida albicans. Mol. Biol. Cell 16, 1971-1986 (2005).
106. Kumamoto, C. A. & Vinces, M. D. Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence. Cell. Microbiol. 7, 1546-1554 (2005).
107. Hnisz, D., Majer, O., Frohner, I. E., Komnenovic, V. & Kuchler, K. The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of Candida albicans. PLoS Pathog. 6, e1000889 (2010).
108. Xu, X. L. et al. Bacterial peptidoglycan triggers Candida albicans hyphal growth by directly activating the adenylyl cyclase Cyr1p. Cell Host Microbe 4, 28-39 (2008).
109. Zou, H., Fang, H. M., Zhu, Y. & Wang, Y. Candida albicans Cyr1, Cap1 and G-actin form a sensor/effector apparatus for activating cAMP synthesis in hyphal growth. Mol. Microbiol. 75, 579-591 (2010).
110. Rodriguez, A., Martinez, I., Chung, A., Berlot, C. H. & Andrews, N. W. cAMP regulates Ca2+-dependent exocytosis of lysosomes and lysosome-mediated cell invasion by trypanosomes. J. Biol. Chem. 274, 16754-16759 (1999).
111. Usynin, I., Klotz, C. & Frevert, U. Malaria circumsporozoite protein inhibits the respiratory burst in Kupffer cells. Cell. Microbiol. 9, 2610-2628 (2007).
112. Ono, T. et al. Adenylyl cyclase α and cAMP signaling mediate Plasmodium sporozoite apical regulated exocytosis and hepatocyte infection. PLoS Pathog. 4, e1000008 (2008).
113. Kebaier, C. & Vanderberg, J. P. Initiation of Plasmodium sporozoite motility by albumin is associated with induction of intracellular signalling. Int. J. Parasitol. 40, 25-33 (2010).
114. Beraldo, F. H., Almeida, F. M., da Silva, A. M. & Garcia, C. R. Cyclic AMP and calcium interplay as second messengers in melatonin-dependent regulation of Plasmodium falciparum cell cycle. J. Cell Biol. 170, 551-557 (2005).
115. Gazarini, M. L. et al. Melatonin triggers PKA activation in the rodent malaria parasite Plasmodium chabaudi. J. Pineal Res. 50, 64-70 (2011).
116. Merckx, A. et al. Plasmodium falciparum regulatory subunit of cAMP-dependent PKA and anion channel conductance. PLoS Pathog. 4, e19 (2008).
117. Leykauf, K. et al. Protein kinase A dependent phosphorylation of apical membrane antigen 1 plays an important role in erythrocyte invasion by the malaria parasite. PLoS Pathog. 6, e1000941 (2010).
118. Dyer, M. & Day, K. Expression of Plasmodium falciparum trimeric G proteins and their involvement in switching to sexual development. Mol. Biochem. Parasitol. 110, 437-448 (2000).
119. Kaushal, D. C., Carter, R., Miller, L. H. & Krishna, G. Gametocytogenesis by malaria parasites in continuous culture. Nature 286, 490-492 (1980).
120. Read, L. K. & Mikkelsen, R. B. Comparison of adenylate cyclase and cAMP-dependent protein kinase in gametocytogenic and nongametocytogenic clones of Plasmodium falciparum. J. Parasitol. 77, 346-352 (1991).
121. Eaton, M. S., Weiss, L. M. & Kim, K. Cyclic nucleotide kinases and tachyzoite-bradyzoite transition in Toxoplasma gondii. Int. J. Parasitol. 36, 107-114 (2006).
122. Bao, Y., Weiss, L. M., Braunstein, V. L. & Huang, H. Role of protein kinase A in Trypanosoma cruzi. Infect. Immun. 76, 4757-4763 (2008).
123. Santos, D. O. & Oliveira, M. M. Effect of cAMP on macromolecule synthesis in the pathogenic protozoa Trypanosoma cruzi. Mem. Inst. Oswaldo Cruz 83, 287-292 (1988).
124. Gonzales-Perdomo, M., Romero, P. & Goldenberg, S. Cyclic AMP and adenylate cyclase activators stimulate Trypanosoma cruzi differentiation. Exp. Parasitol. 66, 205-212 (1988).
125. Rangel-Aldao, R. et al. Cyclic AMP as an inducer of the cell differentiation of Trypanosoma cruzi. Biochem. Int. 17, 337-344 (1988).
126. Schoijet, A. C. et al. Defining the role of a FYVE domain in the localization and activity of a cAMP phosphodiesterase implicated in osmoregulation in Trypanosoma cruzi. Mol. Microbiol. 79, 50-62 (2011).
127. Oberholzer, M. et al. The Trypanosoma brucei cAMP phosphodiesterases TbrPDEB1 and TbrPDEB2: flagellar enzymes that are essential for parasite virulence. FASEB J. 21, 720-731 (2007).
128. Vassella, E., Reuner, B., Yutzy, B. & Boshart, M. Differentiation of African trypanosomes is controlled by a density sensing mechanism which signals cell cycle arrest via the cAMP pathway. J. Cell Sci. 110, 2661-2671 (1997).
129. Bee, A. et al. Transformation of Leishmania mexicana metacyclic promastigotes to amastigote-like forms mediated by binding of human C-reactive protein. Parasitology 122, 521-529 (2001).
130. Rodriguez, M., Kim, B., Lee, N. S., Veeranki, S. & Kim, L. MPL1, a novel phosphatase with leucine-rich repeats, is essential for proper ERK2 phosphorylation and cell motility. Eukaryot. Cell 7, 958-966 (2008).
131. Frederick, J. & Eichinger, D. Entamoeba invadens contains the components of a classical adrenergic signaling system. Mol. Biochem. Parasitol. 137, 339-343 (2004).
132. Swierczewski, B. E. & Davies, S. J. A schistosome cAMP-dependent protein kinase catalytic subunit is essential for parasite viability. PLoS Negl. Trop. Dis. 3, e505 (2009).