Research Overview

Our laboratory pursues both basic and translational studies to understand and treat infections caused by intestinal bacteria. Areas of interest described below include the impact of intestinal pathogens on host metabolism and nutrition, development of biofilm-based antigen and enzyme delivery platforms, and the discovery of novel natural products with antimicrobial activity.

1. The interaction of intestinal pathogens with their hosts on metabolic landscapes. In developing countries, diarrheal disease is a key contributor to malnutrition. We hypothesize that, in addition to increasing stool transit time, diarrheal pathogens modulate host nutrient utilization. Using both invertebrate and vertebrate models to coordinately manipulate host and pathogen genomes, we are exploring the mechanisms by which intestinal pathogens modulate host metabolism.

2. Biofilm matrix-based antigen and enzyme delivery platforms. To form a surface-adherent biofilm, many bacteria require an extracellular matrix comprised of polysaccharides and polysaccharide-binding proteins or lectins. By fusing antigens and enzymes to these lectins, we are constructing self-assembling, whole cell antigen or enzyme oral delivery systems.

3. Discovery of novel therapeutics from natural products to treat multi-drug resistant bacteria. We have developed a high-throughput, whole cell metabolic screen to detect antimicrobial activity. We are currently using this screen to identify natural products that are active against multi-drug resistant bacteria.

About Paula Watnick

Paula Watnick received her PhD from the California Institute of Technology and her M.D. from Yale University. She completed an internship and residency at Beth Israel Hospital, Boston and an Infectious Disease Fellowship at Massachusetts General Hospital. Her postdoctoral research was conducted in the laboratories of Dr. Stephen Calderwood at Massachusetts General Hospital and Dr. Roberto Kolter at Harvard Medical School.

Researcher Services

Researcher Areas

  • Bacterial Adhesion to Surfaces
  • Enteric Pathogens

Research Departments

Research Divisions

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Liao J, Smith DR, Brynjarsdóttir J, Watnick PI. A self-assembling whole cell vaccine antigen presentation platform. J Bacteriol. 2018 Feb 26. View abstract
  2. Kamareddine L, Wong ACN, Vanhove AS, Hang S, Purdy AE, Kierek-Pearson K, Asara JM, Ali A, Morris JG, Watnick PI. Activation of Vibrio cholerae quorum sensing promotes survival of an arthropod host. Nat Microbiol. 2018 Feb; 3(2):243-252. View abstract
  3. Vanhove AS, Hang S, Vijayakumar V, Wong AC, Asara JM, Watnick PI. Vibrio cholerae ensures function of host proteins required for virulence through consumption of luminal methionine sulfoxide. PLoS Pathog. 2017 Jun; 13(6):e1006428. View abstract
  4. Alawdah LS, Campbell JN, Pollock N, Watnick PI. Erysipelothrix rhusiopathiae Suppurative Arthritis in a 12-year-old Boy After an Unusual Fresh Water Exposure. Pediatr Infect Dis J. 2017 Apr; 36(4):431-433. View abstract
  5. Wong AC, Vanhove AS, Watnick PI. The interplay between intestinal bacteria and host metabolism in health and disease: lessons from Drosophila melanogaster. Dis Model Mech. 2016 Mar; 9(3):271-81. View abstract
  6. Leng Y, Vakulskas CA, Zere TR, Pickering BS, Watnick PI, Babitzke P, Romeo T. Regulation of CsrB/C sRNA decay by EIIA(Glc) of the phosphoenolpyruvate: carbohydrate phosphotransferase system. Mol Microbiol. 2016 Feb; 99(4):627-39. View abstract
  7. Smith DR, Maestre-Reyna M, Lee G, Gerard H, Wang AH, Watnick PI. In situ proteolysis of the Vibrio cholerae matrix protein RbmA promotes biofilm recruitment. Proc Natl Acad Sci U S A. 2015 Aug 18; 112(33):10491-6. View abstract
  8. Hang S, Purdy AE, Robins WP, Wang Z, Mandal M, Chang S, Mekalanos JJ, Watnick PI. The acetate switch of an intestinal pathogen disrupts host insulin signaling and lipid metabolism. Cell Host Microbe. 2014 Nov 12; 16(5):592-604. View abstract
  9. Pickering BS, Lopilato JE, Smith DR, Watnick PI. The transcription factor Mlc promotes Vibrio cholerae biofilm formation through repression of phosphotransferase system components. J Bacteriol. 2014 Jul; 196(13):2423-30. View abstract
  10. Guichard A, Cruz-Moreno B, Cruz-Moreno BC, Aguilar B, van Sorge NM, Kuang J, Kurkciyan AA, Wang Z, Hang S, Pineton de Chambrun GP, McCole DF, Watnick P, Nizet V, Bier E. Cholera toxin disrupts barrier function by inhibiting exocyst-mediated trafficking of host proteins to intestinal cell junctions. Cell Host Microbe. 2013 Sep 11; 14(3):294-305. View abstract
  11. Wang Z, Hang S, Purdy AE, Watnick PI. Mutations in the IMD pathway and mustard counter Vibrio cholerae suppression of intestinal stem cell division in Drosophila. MBio. 2013 Jun 18; 4(3):e00337-13. View abstract
  12. Ymele-Leki P, Houot L, Watnick PI. Mannitol and the mannitol-specific enzyme IIB subunit activate Vibrio cholerae biofilm formation. Appl Environ Microbiol. 2013 Aug; 79(15):4675-83. View abstract
  13. Pickering BS, Smith DR, Watnick PI. Glucose-specific enzyme IIA has unique binding partners in the vibrio cholerae biofilm. MBio. 2012 Nov 06; 3(6):e00228-12. View abstract
  14. Absalon C, Ymele-Leki P, Watnick PI. The bacterial biofilm matrix as a platform for protein delivery. MBio. 2012; 3(4):e00127-12. View abstract
  15. Wang Z, Berkey CD, Watnick PI. The Drosophila protein mustard tailors the innate immune response activated by the immune deficiency pathway. J Immunol. 2012 Apr 15; 188(8):3993-4000. View abstract
  16. Ymele-Leki P, Cao S, Sharp J, Lambert KG, McAdam AJ, Husson RN, Tamayo G, Clardy J, Watnick PI. A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity. PLoS One. 2012; 7(2):e31307. View abstract
  17. Purdy AE, Watnick PI. Spatially selective colonization of the arthropod intestine through activation of Vibrio cholerae biofilm formation. Proc Natl Acad Sci U S A. 2011 Dec 06; 108(49):19737-42. View abstract
  18. Absalon C, Van Dellen K, Watnick PI. A communal bacterial adhesin anchors biofilm and bystander cells to surfaces. PLoS Pathog. 2011 Aug; 7(8):e1002210. View abstract
  19. Houot L, Chang S, Pickering BS, Absalon C, Watnick PI. The phosphoenolpyruvate phosphotransferase system regulates Vibrio cholerae biofilm formation through multiple independent pathways. J Bacteriol. 2010 Jun; 192(12):3055-67. View abstract
  20. Houot L, Chang S, Absalon C, Watnick PI. Vibrio cholerae phosphoenolpyruvate phosphotransferase system control of carbohydrate transport, biofilm formation, and colonization of the germfree mouse intestine. Infect Immun. 2010 Apr; 78(4):1482-94. View abstract
  21. Karatan E, Watnick P. Signals, regulatory networks, and materials that build and break bacterial biofilms. Microbiol Mol Biol Rev. 2009 Jun; 73(2):310-47. View abstract
  22. Berkey CD, Blow N, Watnick PI. Genetic analysis of Drosophila melanogaster susceptibility to intestinal Vibrio cholerae infection. Cell Microbiol. 2009 Mar; 11(3):461-74. View abstract
  23. Van Dellen KL, Houot L, Watnick PI. Genetic analysis of Vibrio cholerae monolayer formation reveals a key role for DeltaPsi in the transition to permanent attachment. J Bacteriol. 2008 Dec; 190(24):8185-96. View abstract
  24. Houot L, Watnick PI. A novel role for enzyme I of the Vibrio cholerae phosphoenolpyruvate phosphotransferase system in regulation of growth in a biofilm. J Bacteriol. 2008 Jan; 190(1):311-20. View abstract
  25. Karatan E, Duncan TR, Watnick PI. NspS, a predicted polyamine sensor, mediates activation of Vibrio cholerae biofilm formation by norspermidine. J Bacteriol. 2005 Nov; 187(21):7434-43. View abstract
  26. Blow NS, Salomon RN, Garrity K, Reveillaud I, Kopin A, Jackson FR, Watnick PI. Vibrio cholerae infection of Drosophila melanogaster mimics the human disease cholera. PLoS Pathog. 2005 Sep; 1(1):e8. View abstract
  27. Moorthy S, Watnick PI. Identification of novel stage-specific genetic requirements through whole genome transcription profiling of Vibrio cholerae biofilm development. Mol Microbiol. 2005 Sep; 57(6):1623-35. View abstract
  28. Kapfhammer D, Karatan E, Pflughoeft KJ, Watnick PI. Role for glycine betaine transport in Vibrio cholerae osmoadaptation and biofilm formation within microbial communities. Appl Environ Microbiol. 2005 Jul; 71(7):3840-7. View abstract
  29. Moorthy S, Watnick PI. Genetic evidence that the Vibrio cholerae monolayer is a distinct stage in biofilm development. Mol Microbiol. 2004 Apr; 52(2):573-87. View abstract
  30. Kierek K, Watnick PI. The Vibrio cholerae O139 O-antigen polysaccharide is essential for Ca2+-dependent biofilm development in sea water. Proc Natl Acad Sci U S A. 2003 Nov 25; 100(24):14357-62. View abstract
  31. Pflughoeft KJ, Kierek K, Watnick PI. Role of ectoine in Vibrio cholerae osmoadaptation. Appl Environ Microbiol. 2003 Oct; 69(10):5919-27. View abstract
  32. Kierek K, Watnick PI. Environmental determinants of Vibrio cholerae biofilm development. Appl Environ Microbiol. 2003 Sep; 69(9):5079-88. View abstract
  33. Bomchil N, Watnick P, Kolter R. Identification and characterization of a Vibrio cholerae gene, mbaA, involved in maintenance of biofilm architecture. J Bacteriol. 2003 Feb; 185(4):1384-90. View abstract
  34. Haugo AJ, Watnick PI. Vibrio cholerae CytR is a repressor of biofilm development. Mol Microbiol. 2002 Jul; 45(2):471-83. View abstract
  35. Watnick PI. Paula I Watnick--elucidating the role of biofilms. Interview by Pam Das. Lancet Infect Dis. 2002 Mar; 2(3):190-2. View abstract
  36. Watnick PI, Lauriano CM, Klose KE, Croal L, Kolter R. The absence of a flagellum leads to altered colony morphology, biofilm development and virulence in Vibrio cholerae O139. Mol Microbiol. 2001 Jan; 39(2):223-35. View abstract
  37. Watnick P, Kolter R. Biofilm, city of microbes. J Bacteriol. 2000 May; 182(10):2675-9. View abstract
  38. Butterton JR, Choi MH, Watnick PI, Carroll PA, Calderwood SB. Vibrio cholerae VibF is required for vibriobactin synthesis and is a member of the family of nonribosomal peptide synthetases. J Bacteriol. 2000 Mar; 182(6):1731-8. View abstract
  39. Watnick PI, Kolter R. Steps in the development of a Vibrio cholerae El Tor biofilm. Mol Microbiol. 1999 Nov; 34(3):586-95. View abstract
  40. Watnick PI, Fullner KJ, Kolter R. A role for the mannose-sensitive hemagglutinin in biofilm formation by Vibrio cholerae El Tor. J Bacteriol. 1999 Jun; 181(11):3606-9. View abstract
  41. O'Toole GA, Pratt LA, Watnick PI, Newman DK, Weaver VB, Kolter R. Genetic approaches to study of biofilms. Methods Enzymol. 1999; 310:91-109. View abstract
  42. Watnick PI, Butterton JR, Calderwood SB. The interaction of the Vibrio cholerae transcription factors, Fur and IrgB, with the overlapping promoters of two virulence genes, irgA and irgB. Gene. 1998 Mar 16; 209(1-2):65-70. View abstract
  43. Watnick PI, Eto T, Takahashi H, Calderwood SB. Purification of Vibrio cholerae fur and estimation of its intracellular abundance by antibody sandwich enzyme-linked immunosorbent assay. J Bacteriol. 1997 Jan; 179(1):243-7. View abstract
  44. Watnick PI, Chan SI, Dea P. Hydrophobic mismatch in gramicidin A'/lecithin systems. Biochemistry. 1990 Jul 03; 29(26):6215-21. View abstract
  45. Watnick PI, Dea P, Chan SI. Characterization of the transverse relaxation rates in lipid bilayers. Proc Natl Acad Sci U S A. 1990 Mar; 87(6):2082-6. View abstract
  46. Gierasch LM, Lacy JE, Thompson KF, Rockwell AL, Watnick PI. Conformations of model peptides in membrane-mimetic environments. Biophys J. 1982 Jan; 37(1):275-84. View abstract