Dept. of Microbiology and
Harvard Medical School
NRB, Room 1035A
77 Avenue Louis Pasteur
Boston, MA 02115
Mekalanos Lab Home
The Mekalanos laboratory is primarily engaged in the biochemical and genetic analysis of bacterial virulence factors. The long-term goal of these studies is to understand how pathogenic bacteria evade the host immune system and ultimately cause disease. While a variety of organisms are currently being studied in the laboratory (e.g. Helicobacter pylori, Pseudomonas aeruginosa, Haemophilus influenzae, and E. coli) the longest ongoing research project concerns the bacterium Vibrio cholerae. This organism produces an adenylate cyclase-activating toxin which has effects on the physiology of the intestine and enhances the colonization of the intestine. While cholera toxin is the most-studied virulence factor, strains lacking cholera toxin still cause symptoms. Recent work has identified a novel toxin that may be partly responsible for this; the mechanism by which this occurs is currently under investigation.
The Mekalanos lab has recently developed a variety of new genetic strategies for identifying genes required for survival of bacteria in vitro and in vivo. Some of these genes have turned out to be essential for infection and/or virulence. Understanding the molecular mechanism of how these gene products are regulated in vivo and the role that these regulatory responses play in pathogenesis are long term goals of the laboratory. Where possible, the knowledge gained in these studies will be applied to the development of more effective vaccines for bacterial diseases and the identification of new targets for antimicrobial drug development. We have also discovered novel toxins and protein secretion systems that may be partly responsible for virulence in vivo which are currently under investigation.
Type VI secretion system sheaths as nanoparticles for antigen display.
Del Tordello E, Danilchanka O, McCluskey AJ, Mekalanos JJ. Proc Natl Acad Sci U S A. 2016 Feb 29. pii: 201524290.
Emergence of Antimicrobial-Resistant Escherichia coli of Animal Origin Spreading in Humans. Skurnik D, Clermont O, Guillard T, Launay A, Danilchanka O, Pons S, Diancourt L, Lebreton F, Kadlec K, Roux D, Jiang D, Dion S, Aschard H, Denamur M, Cywes-Bentley C, Schwarz S, Tenaillon O, Andremont A, Picard B, Mekalanos J, Brisse S, Denamur E. Mol Biol Evol. 2016 Apr;33(4):898-914. doi: 10.1093/molbev/msv280. Epub 2015 Nov 26.
Fitness cost of antibiotic susceptibility during bacterial infection.
Roux D, Danilchanka O, Guillard T, Cattoir V, Aschard H, Fu Y, Angoulvant F, Messika J, Ricard JD, Mekalanos JJ, Lory S, Pier GB, Skurnik D. Sci Transl Med. 2015 Jul 22;7(297):297ra114. doi: 10.1126/scitranslmed.aab1621.
Secretome analysis of Vibrio cholerae type VI secretion system reveals a new effector-immunity pair. Altindis E, Dong T, Catalano C, Mekalanos J. MBio. 2015 Mar 10;6(2):e00075. doi: 10.1128/mBio.00075-15.
Conjugate-like immunogens produced as protein capsular matrix vaccines. Thanawastien A, Cartee RT, Griffin TJ 4th, Killeen KP, Mekalanos JJ. Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):E1143-51. doi: 10.1073/pnas.1425005112. Epub 2015 Feb 19.
Generation of reactive oxygen species by lethal attacks from competing microbes. Dong TG, Dong S, Catalano C, Moore R, Liang X, Mekalanos JJ. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2181-6. doi: 10.1073/pnas.1425007112. Epub 2015 Feb 2.
The acetate switch of an intestinal pathogen disrupts host insulin signaling and lipid metabolism. Hang S, Purdy AE, Robins WP, Wang Z, Mandal M, Chang S, Mekalanos JJ, Watnick PI. Cell Host Microbe. 2014 Nov 12;16(5):592-604. doi: 10.1016/j.chom.2014.10.006. Epub 2014 Nov 12.
Vibrio cholerae T3SS effector VopE modulates mitochondrial dynamics and innate immune signaling by targeting Miro GTPases. Suzuki M, Danilchanka O, Mekalanos JJ. Cell Host Microbe. 2014 Nov 12;16(5):581-91. doi: 10.1016/j.chom.2014.09.015. Epub 2014 Oct 23.
RS1 satellite phage promotes diversity of toxigenic Vibrio cholerae by driving CTX prophage loss and elimination of lysogenic immunity. Kamruzzaman M, Robins WP, Bari SM, Nahar S, Mekalanos JJ, Faruque SM. Infect Immun. 2014 Sep;82(9):3636-43. doi: 10.1128/IAI.01699-14. Epub 2014 Jun 16.
The highly conserved bacterial RNase YbeY is essential in Vibrio cholerae, playing a critical role in virulence, stress regulation, and RNA processing. Vercruysse M, Köhrer C, Davies BW, Arnold MF, Mekalanos JJ, RajBhandary UL, Walker GC. PLoS Pathog. 2014 Jun 5;10(6):e1004175. doi: 10.1371/journal.ppat.1004175. eCollection 2014 Jun.
Proteomic analysis of Vibrio cholerae outer membrane vesicles. Altindis E, Fu Y, Mekalanos JJ. Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):E1548-56. doi: 10.1073/pnas.1403683111. Epub 2014 Mar 31.
Vibrio parahaemolyticus and its specific bacteriophages as an indicator in cockles (Anadara granosa) for the risk of V. parahaemolyticus infection in Southern Thailand. Yingkajorn M, Sermwitayawong N, Palittapongarnpimp P, Nishibuchi M, Robins WP, Mekalanos JJ, Vuddhakul V. Microb Ecol. 2014 May;67(4):849-56. doi: 10.1007/s00248-014-0382-9. Epub 2014 Feb 28.