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John J. Mekalanos

Education

Ph.D. in Microbiology, University of California, Los Angeles, 1978

Current position

Professor and Chair, Department of Microbiology and Immunobiology (formerly Microbiology and Molecular Genetics), Harvard Medical School, Boston, MA (2011-present)

Publications

Original research articles

  1. Yingkajorn, M., Sermwitayawong, N., Palittapongarnpimp, P., Nishibuchi, M., Robins, W. P., Mekalanos, J. J. and Vuddhakul, V. (2014). Vibrio parahaemolyticus and its specific bacteriophages as an indicator in cockles (Anadara granosa) for the risk of V. parahaemolyticus infection in Southern Thailand. Microb Ecol 67(4): 849-856.
  2. Altindis, E., Fu, Y. and Mekalanos, J. J. (2014). Proteomic analysis of Vibrio cholerae outer membrane vesicles. Proc Natl Acad Sci U S A 111(15): E1548-1556.
  3. Robins, W. P. and Mekalanos, J. J. (2014). Genomic Science in Understanding Cholera Outbreaks and Evolution of Vibrio cholerae as a Human Pathogen. Curr Top Microbiol Immunol.
  4. Ho, B. T., Dong, T. G. and Mekalanos, J. J. (2014). A view to a kill: the bacterial type VI secretion system. Cell Host Microbe 15(1): 9-21.
  5. Fu, Y., Waldor, M. K. and Mekalanos, J. J. (2013). Tn-Seq analysis of Vibrio cholerae intestinal colonization reveals a role for T6SS-mediated antibacterial activity in the host. Cell Host Microbe 14(6): 652-663.
  6. Skurnik, D., Roux, D., Cattoir, V., Danilchanka, O., Lu, X., Yoder-Himes, D. R., Han, K., Guillard, T., Jiang, D., Gaultier, C., Guerin, F., Aschard, H., Leclercq, R., Mekalanos, J. J., Lory, S. and Pier, G. B. (2013). Enhanced in vivo fitness of carbapenem-resistant oprD mutants of Pseudomonas aeruginosa revealed through high-throughput sequencing. Proc Natl Acad Sci U S A 110(51): 20747-20752.
  7. Ho, B. T., Basler, M. and Mekalanos, J. J. (2013). Type 6 secretion system-mediated immunity to type 4 secretion system-mediated gene transfer. Science 342(6155): 250-253.
  8. Mekalanos, J. J. (2013). Vaccine economics: what price human life? Sci Transl Med 5(204): 204ed216.
  9. Danilchanka, O. and Mekalanos, J. J. (2013). Cyclic dinucleotides and the innate immune response. Cell 154(5): 962-970.
  10. Shneider, M. M., Buth, S. A., Ho, B. T., Basler, M., Mekalanos, J. J. and Leiman, P. G. (2013). PAAR-repeat proteins sharpen and diversify the type VI secretion system spike. Nature 500(7462): 350-353.
  11. Bari, S. M., Roky, M. K., Mohiuddin, M., Kamruzzaman, M., Mekalanos, J. J. and Faruque, S. M. (2013). Quorum-sensing autoinducers resuscitate dormant Vibrio cholerae in environmental water samples. Proc Natl Acad Sci U S A 110(24): 9926-9931.
  12. Basler, M., Ho, B. T. and Mekalanos, J. J. (2013). Tit-for-tat: type VI secretion system counterattack during bacterial cell-cell interactions. Cell 152(4): 884-894.
  13. Robins, W. P., Faruque, S. M. and Mekalanos, J. J. (2013). Coupling mutagenesis and parallel deep sequencing to probe essential residues in a genome or gene. Proc Natl Acad Sci U S A 110(9): E848-857.
  14. Dong, T. G., Ho, B. T., Yoder-Himes, D. R. and Mekalanos, J. J. (2013). Identification of T6SS-dependent effector and immunity proteins by Tn-seq in Vibrio cholerae. Proc Natl Acad Sci U S A 110(7): 2623-2628.
  15. Faruque, S. M. and Mekalanos, J. J. (2012). Phage-bacterial interactions in the evolution of toxigenic Vibrio cholerae. Virulence 3(7): 556-565.
  16. Mekalanos, J. J., Robins, W., Ussery, D. W., Davis, B. M., Schadt, E. and Waldor, M. K. (2012). Non-O1 Vibrio cholerae unlinked to cholera in Haiti. Proc Natl Acad Sci U S A 109(47): E3206; author reply E3207.
  17. Seed, K. D., Faruque, S. M., Mekalanos, J. J., Calderwood, S. B., Qadri, F. and Camilli, A. (2012). Phase variable O antigen biosynthetic genes control expression of the major protective antigen and bacteriophage receptor in Vibrio cholerae O1. PLoS Pathog 8(9): e1002917.
  18. Bogard, R. W., Davies, B. W. and Mekalanos, J. J. (2012). MetR-regulated Vibrio cholerae metabolism is required for virulence. MBio 3(5).
  19. Basler, M. and Mekalanos, J. J. (2012). Type 6 secretion dynamics within and between bacterial cells. Science 337(6096): 815.
  20. Bashir, A., Klammer, A. A., Robins, W. P., Chin, C. S., Webster, D., Paxinos, E., Hsu, D., Ashby, M., Wang, S., Peluso, P., Sebra, R., Sorenson, J., Bullard, J., Yen, J., Valdovino, M., Mollova, E., Luong, K., Lin, S., LaMay, B., Joshi, A., Rowe, L., Frace, M., Tarr, C. L., Turnsek, M., Davis, B. M., Kasarskis, A., Mekalanos, J. J., Waldor, M. K. and Schadt, E. E. (2012). A hybrid approach for the automated finishing of bacterial genomes. Nat Biotechnol 30(7): 701-707.
  21. Dong, T. G. and Mekalanos, J. J. (2012). Characterization of the RpoN regulon reveals differential regulation of T6SS and new flagellar operons in Vibrio cholerae O37 strain V52. Nucleic Acids Res 40(16): 7766-7775.
  22. Davies, B. W., Bogard, R. W., Young, T. S. and Mekalanos, J. J. (2012). Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence. Cell 149(2): 358-370.
  23. Basler, M., Pilhofer, M., Henderson, G. P., Jensen, G. J. and Mekalanos, J. J. (2012). Type VI secretion requires a dynamic contractile phage tail-like structure. Nature 483(7388): 182-186.
  24. Rattanama, P., Thompson, J. R., Kongkerd, N., Srinitiwarawong, K., Vuddhakul, V. and Mekalanos, J. J. (2012). Sigma E regulators control hemolytic activity and virulence in a shrimp pathogenic Vibrio harveyi. PLoS One 7(2): e32523.
  25. Mandlik, A., Livny, J., Robins, W. P., Ritchie, J. M., Mekalanos, J. J. and Waldor, M. K. (2011). RNA-Seq-based monitoring of infection-linked changes in Vibrio cholerae gene expression. Cell Host Microbe 10(2): 165-174.
  26. Davies, B. W., Bogard, R. W. and Mekalanos, J. J. (2011). Mapping the regulon of Vibrio cholerae ferric uptake regulator expands its known network of gene regulation. Proc Natl Acad Sci U S A 108(30): 12467-12472.
  27. Shin, O. S., Tam, V. C., Suzuki, M., Ritchie, J. M., Bronson, R. T., Waldor, M. K. and Mekalanos, J. J. (2011). Type III secretion is essential for the rapidly fatal diarrheal disease caused by non-O1, non-O139 Vibrio cholerae. MBio 2(3): e00106-00111.
  28. Zheng, J., Ho, B. and Mekalanos, J. J. (2011). Genetic analysis of anti-amoebae and anti-bacterial activities of the type VI secretion system in Vibrio cholerae. PLoS One 6(8): e23876.
  29. Rao, J., Damron, F. H., Basler, M., Digiandomenico, A., Sherman, N. E., Fox, J. W., Mekalanos, J. J. and Goldberg, J. B. (2011). Comparisons of Two Proteomic Analyses of Non-Mucoid and Mucoid Pseudomonas aeruginosa Clinical Isolates from a Cystic Fibrosis Patient. Front Microbiol 2: 162.
  30. Farmer, P., Almazor, C. P., Bahnsen, E. T., Barry, D., Bazile, J., Bloom, B. R., Bose, N., Brewer, T., Calderwood, S. B., Clemens, J. D., Cravioto, A., Eustache, E., Jerome, G., Gupta, N., Harris, J. B., Hiatt, H. H., Holstein, C., Hotez, P. J., Ivers, L. C., Kerry, V. B., Koenig, S. P., Larocque, R. C., Leandre, F., Lambert, W., Lyon, E., Mekalanos, J. J., Mukherjee, J. S., Oswald, C., Pape, J. W., Gretchko Prosper, A., Rabinovich, R., Raymonville, M., Rejouit, J. R., Ronan, L. J., Rosenberg, M. L., Ryan, E. T., Sachs, J. D., Sack, D. A., Surena, C., Suri, A. A., Ternier, R., Waldor, M. K., Walton, D. and Weigel, J. L. (2011). Meeting cholera's challenge to Haiti and the world: a joint statement on cholera prevention and care. PLoS Negl Trop Dis 5(5): e1145.
  31. Zahid, M. S., Waise, Z., Kamruzzaman, M., Ghosh, A. N., Nair, G. B., Khairul Bashar, S. A., Mekalanos, J. J. and Faruque, S. M. (2011). An experimental study of phage mediated bactericidal selection & emergence of the El Tor Vibrio cholerae. Indian J Med Res 133: 218-224.
  32. Davies, B. W., Bogard, R. W., Dupes, N. M., Gerstenfeld, T. A., Simmons, L. A. and Mekalanos, J. J. (2011). DNA damage and reactive nitrogen species are barriers to Vibrio cholerae colonization of the infant mouse intestine. PLoS Pathog 7(2): e1001295.
  33. Chin, C. S., Sorenson, J., Harris, J. B., Robins, W. P., Charles, R. C., Jean-Charles, R. R., Bullard, J., Webster, D. R., Kasarskis, A., Peluso, P., Paxinos, E. E., Yamaichi, Y., Calderwood, S. B., Mekalanos, J. J., Schadt, E. E. and Waldor, M. K. (2011). The origin of the Haitian cholera outbreak strain. N Engl J Med 364(1): 33-42.
  34. Tam, V. C., Suzuki, M., Coughlin, M., Saslowsky, D., Biswas, K., Lencer, W. I., Faruque, S. M. and Mekalanos, J. J. (2010). Functional analysis of VopF activity required for colonization in Vibrio cholerae. MBio 1(5).
  35. Zheng, J., Shin, O. S., Cameron, D. E. and Mekalanos, J. J. (2010). Quorum sensing and a global regulator TsrA control expression of type VI secretion and virulence in Vibrio cholerae. Proc Natl Acad Sci U S A 107(49): 21128-21133.
  36. Hassan, F., Kamruzzaman, M., Mekalanos, J. J. and Faruque, S. M. (2010). Satellite phage TLCphi enables toxigenic conversion by CTX phage through dif site alteration. Nature 467(7318): 982-985.
  37. Zahid, M. S., Waise, T. M., Kamruzzaman, M., Ghosh, A. N., Nair, G. B., Mekalanos, J. J. and Faruque, S. M. (2010). The cyclic AMP (cAMP)-cAMP receptor protein signaling system mediates resistance of Vibrio cholerae O1 strains to multiple environmental bacteriophages. Appl Environ Microbiol 76(13): 4233-4240.
  38. Rui, H., Ritchie, J. M., Bronson, R. T., Mekalanos, J. J., Zhang, Y. and Waldor, M. K. (2010). Reactogenicity of live-attenuated Vibrio cholerae vaccines is dependent on flagellins. Proc Natl Acad Sci U S A 107(9): 4359-4364.
  39. Ma, A. T. and Mekalanos, J. J. (2010). In vivo actin cross-linking induced by Vibrio cholerae type VI secretion system is associated with intestinal inflammation. Proc Natl Acad Sci U S A 107(9): 4365-4370.
  40. Kamruzzaman, M., Udden, S. M., Cameron, D. E., Calderwood, S. B., Nair, G. B., Mekalanos, J. J. and Faruque, S. M. (2010). Quorum-regulated biofilms enhance the development of conditionally viable, environmental Vibrio cholerae. Proc Natl Acad Sci U S A 107(4): 1588-1593.
  41. Flier, J. S. and Mekalanos, J. J. (2009). Gut check: testing a role for the intestinal microbiome in human obesity. Sci Transl Med 1(6): 6ps7.
  42. Thanawastien, A., Montor, W. R., Labaer, J., Mekalanos, J. J. and Yoon, S. S. (2009). Vibrio cholerae proteome-wide screen for immunostimulatory proteins identifies phosphatidylserine decarboxylase as a novel Toll-like receptor 4 agonist. PLoS Pathog 5(8): e1000556.
  43. Ma, A. T., McAuley, S., Pukatzki, S. and Mekalanos, J. J. (2009). Translocation of a Vibrio cholerae type VI secretion effector requires bacterial endocytosis by host cells. Cell Host Microbe 5(3): 234-243.

Book chapters and symposium volumes

  1. Faruque, S. and Mekalanos, J. J. (2008). Molecular Ecology of Vibrio cholerae. In: Faruque, S. M. and Nair, G. B. (eds). Vibrio cholerae: Genomics and Molecular Biology.Horizon Scientific Press.
  2. Zhu, J. and Mekalanos, J. J. (2006). Quorum-sensing-mediated regulation of biofilm growth and virulence of Vibrio cholerae. In: Demuth, D. R. and Lamont, R. J. (eds). Bacterial Cell-to-Cell Communication: Role in Virulence and Pathogenesis. Cambridge University Press.
  3. Camilli, A., Merrell, D. S. and Mekalanos, J. J. (2001). Strategies to Identify Bacterial Pathogenicity Factors. In: Groisman, E. A. (ed). Principles of Bacterial Pathogenesis. Academic Press.
  4. Hase, C. C., Judson, N. and Mekalanos, J. J. (2000). Cholera. In: Lederberg, J. (ed). Encyclopedia of Microbiology. Academic Press, Volume 1.
  5. Lee, C. and Mekalanos, J. (1999). Bacterial interactions with intestinal epithelial cells. In: Ogra, P. L. et al. (eds). Mucosal Immunology. Academic Press.
  6. Chiang, S. L., Mekalanos, J. J. and Holden, D. W. (1999). In vivo genetic analysis of bacterial virulence. In: Ornston, L. N. and A Balows, A. and Greenberg, E. P. (eds), Annual Reviews of Microbiology. Volume 53.
  7. Rubin, E. J., Waldor, M. K., Mekalanos, J. J. (1998). Mobile genetic elements and the evolution of new epidemic strains of V. cholerae. In: Krause, R. M. (ed). Emerging Infectious Diseases. Academic Press.
  8. Waldor, M. K., Lazar, S., Kimsey, H., Williams, J., Mekalanos, J. J. (1998). CTXφ: A novel filamentous phae encoding cholera toxin. In: Hacker et al. (eds). Bacterial Protein Toxins. Gustav Fischer.
  9. Killeen, K., Spriggs, D. and Mekalanos, J. (1998). Bacterial mucosal vaccines: Vibrtio cholerae as a live attenuated vaccine/vector paradigm. In: Kraehenbuhl, J. P. and Neutra, M. R. (eds). Defense of Mucosal Surfaces: Pathogenesis, Immunity and Vaccines. Springer.
  10. Chiang, S. L. and Mekalanos, J. J. (1998). Horizontal gene transfer in the emergence of virulent Vibrio cholerae. In: Rosenberg, E. (ed). Microbial Ecology and Infectious Diseases. ASM Press.
  11. Mahan, M. J., Slauch, J. M. and Mekalanos, J. J. (1996). Environmental regulation of virulence gene expression in Escherichia, Salmonella, and Shigella. In: Neidhardt, F. C., Ingraham, J. L., Low, K. B., Magasanik, B., Schaechter, M. and Umbarger, H. E. (eds). Escherichia coli and Salmonella typhimurium Cellular and Molecular Biology. American Society for Microbiology, 2803-2815.
  12. Waldor, M. K. and Mekalanos, J. J. (1996). Vibrio cholerae: Molecular pathogenesis, immune response, and vaccine development. In: Paradise, L. J. et al. (eds). Enteric Infections and Immunity. Plenum Press, 37-56.
  13. Dziejman, M. and Mekalanos, J. J. (1995). Two-component signal transduction and its role in the expression of bacterial virulence factors. In: Hoch, J. A. and Silhavy, T. J. (eds). Two-component Signal Transduction. American Society for Microbiology, 305-317.
  14. Mahan, M. J., Slauch, J. M., Hanna, P. C., Camilli, A. C., Tobias, J. W., Waldor, M. K. and Mekalanos, J. J. (1994). Selection for bacterial virulence genes that are specifically induced in host tissues: The hunt for virulence factors. In: Falkow, S. (ed). Infectious Agents and Diseases. Raven Press, Volume II. 2:263-268.
  15. Ottemann, K. M. and Mekalanos, J. J. (1994). Regulation of Cholera Toxin Expression. In: Wachsmuth, K., Blake, P. A. and Olsivk, O. (eds). Vibrio cholerae and Cholera: Molecular to Global Perspectives. American Society for Microbiology, 177-185.
  16. Slauch, J. M., Mahan, M. J. and Mekalanos, J. J. (1994). In vivo expression technology for selection bacterial genes specifically induced in host tissues. In: Clark, V. L. and Bavoil, P. M. (eds). Methods in Enzymology. Academic Press, Vol. 235. 481-492.
  17. Gardel, C. L. and Mekalanos, J. J. (1994). Regulation of cholera toxin by temperature, pH, and osmolarity. In: Clark, V. L. and Bavoil, P. M. (eds). Methods in Enzymology. Academic Press, Vol. 235. 517-526.
  18. Mahan, M. J., Slauch, J. M. and Mekalanos, J. J. (1993). Selection for Bacterial Virulence Genes that are Specifically Induced in Animal Tissues. In: Cabello, F. (ed). The Biology of Salmonella. Plenum Publishing Corporation, 131-139.
  19. Slauch, J. M., Mahan, M. J., Michetti, P., Neutra, M. R. and Mekalanos, J. J. (1993). Mucosal Immunity: The Role of Secretory Immunoglobulin A in Protection Against the Invasive Pathogen Salmonella typimurium. In: Cabello, F. (ed). The Biology of Salmonella. Plenum Publishing Corporation, 289-298.
  20. Mekalanos, J. J. (1992). Bacterial Mucosal Vaccines. In: Ciardi, J. E., McGhee, J. R. and Keith, J. M. (eds). Advances in Experimental Medicine and Biology Volume 327: Genetically Engineered Vaccines. Plenum Publishing Corporation, 43-50.
  21. Mekalanos, J. J. and DiRita, V. J. (1990). Signal transduction in the control of cholera toxin expression. In: Moss, J. and Vaughan, M. (eds). ADP-Ribosylating Toxins and G. Proteins: Insights into Signal Transduction. American Society for Microbiology, 117-126.
  22. Finn, E., Beattie, D., Knapp, S., Capiau, C., Simoen, E. and Mekalanos, J.J. (1990). Coordinate Regulation in Bordetella pertussis. In: Rappouli, R., Alouf, J. E., Falmagne, P., Fehrenbach, F. J., Freer, J., Gross, R., Jeljaszewicz, J., Montecucco, C., Tomasi, M., Wadstrom, T. and Witholt, B. (eds). Bacterial Protein Toxins, Fourth European Workshop. Gustav Fischer, 303-308.
  23. DiRita, V. J., Peterson, K. M. and Mekalanos, J. J. (1990). Regulation of cholera toxin synthesis. In: Iglewski, B. H., Clark, V. L. (eds). Molecular Basis of Pathogenesis. Academic Press, 355-376.
  24. Shaw, C. E., Peterson, K. M., Mekalanos, J. J. and Taylor, R. K. (1989). Genetic studies of Vibrio cholerae TCP pilus biogenesis. In: Kuwahara, S. and Pierce, N. F. (eds). Advances in Research on Cholera and Related Diarrheas. KTK Sci. Pub, Vol. 6.
  25. Taylor, R. K., Guo, Z. and Mekalanos, J. J. (1988). Genetic analysis of extracellularly secreted proteins of Vibrio cholerae. In: Kuwahara, S. and Pierce, N. F. (eds). Advances in Research and Cholera and Related Diarrheas. KTK Sc. Pub., Vol. 5. 127-135.
  26. Mekalanos, J. J. (1988). Production and purification of cholera toxin. In: Harshman, S. (ed). Methods in Enzymology. Academic Press, Inc., Vol. 165. 169-175.
  27. Calderwood, S., Knapp, S., Peterson, K., Taylor, R. and Mekalanos, J. J. (1988). Coordinate regulation of virulence determinants In: Fehrenbach, F. J., Alouf, J. E., Falmagne, P., Goebel, W., Jeljaszewicx, J., Jurgens, D. and Rappouli, R. (eds). Bacterial Protein Toxins, Third European Workshop. Gustav Fischer, 169-175.
  28. Mekalanos, J. J., Pearson, G. D. N., Swartz, D. J., Miller, V. L., Sporecke, I., Harford, N., Groyne, F. and DeWilde, M. (1986). Cholera toxin genes: Detailed genetic analysis and construction of vaccine strains. In: Vol. 3. Kuwahara, S. and Pierce, N. F. (eds). Advances in Research on Cholera and Related Diarrheas. KTK Sci. Pub., 169-180.
  29. Mekalanos, J. J., Miller, V. M., Taylor, R. T. and Goldberg, I. (1986). Genetics of cholera toxin. In: Lark, D. L. (ed). Protein-Carbohydrate Interactions in Biological Systems. The Molecular Biology of Microbial Pathogenicity. Academic Press, 407-413.
  30. Taylor, R. K., Miller, V. L., Furlong, D. B. and Mekalanos, J. J. (1986). Identification of a pilus colonization factor that is coordinatley regulated with cholera toxin. In: Tagliabue, A., Rappouli, R. and Piazzi, S. E. (eds). Bacterial Vaccines and Local Immunity. Annali Sclavo - Collana Monografica. 3:51-61.
  31. Mekalanos, J. J., Goldbert, I., Miller, V., Pearson, G., Swartz, D., Taylor, R., Harford, N., Gathoye, A., Simoen, E., Boon, B. and DeWilde, M. (1985). Genetic construction of cholera vaccine prototypes. In: Lerner, R., Chanock, R. and Brown, F. (eds). Vaccines 85. Cold Spring Harbor Press, 101-105.
  32. Mekalanos, J. J. (1985). Cholera toxin: genetic analysis, regulation, and role in pathogenesis. In: Goebel, W. (ed). Genetic Approaches to Bacterial Pathogenicity. Current Topics in Microbiology and Immunology. Springer, 118:97-118.
  33. Mekalanos, J. J. (1984). The molecular genetics of cholera toxin. In: Colwell, R. (ed). Vibrios in the Environment. John Wiley & Sons, Inc., 195-203.
  34. Collier, R. J. and Mekalanos, J. J. (1980). ADP-ribosylating exotoxins. In: Bisswanger, H. and Schmincke-Ott, E. (eds). Multi-functional Proteins. John Wiley & Sons, Inc., 261-291.
  35. Mekalanos, J. J. and Murphy, J. R. (1979). Regulation of cholera toxin production in Vibrio cholerae: Interactions between hypotoxinogenic and hypertoxinogenic recombinants. Proceedings of the 15th Joint Conference on Cholera. United States-Japan Cooperative Medical Science Program, National Institutes of Health, Bethesda, MD.
Protocols by John J. Mekalanos
  1. Infant Rabbit Colonization Competition Assays