Research

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Paula I.  Watnick, MD, PhD

Paula I. Watnick
Department:
Medicine Research
Division
Infectious Diseases Research
Hospital Title:
Senior Associate Physician in Medicine
Academic Title:
Associate Professor of Pediatrics, Harvard Medical School
Research Focus Area:
Bacterial adhesion to surfacesenteric pathogens
Contact Via Email
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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.

Publications

Publications powered by Harvard Catalyst Profiles
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Absalon C, Ymele-Leki P, Watnick PI. The bacterial biofilm matrix as a platform for protein delivery. MBio. 2012; 3(4):e00127-12.
  10. 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.
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  12. 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.
  13. 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 6; 108(49):19737-42.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. Kierek K, Watnick PI. Environmental determinants of Vibrio cholerae biofilm development. Appl Environ Microbiol. 2003 Sep; 69(9):5079-88.
  21. 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.
  22. Watnick P, Kolter R. Biofilm, city of microbes. J Bacteriol. 2000 May; 182(10):2675-9.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. Pflughoeft KJ, Kierek K, Watnick PI. Role of ectoine in Vibrio cholerae osmoadaptation. Appl Environ Microbiol. 2003 Oct; 69(10):5919-27.
  31. Watnick PI. Paula I Watnick--elucidating the role of biofilms. Interview by Pam Das. Lancet Infect Dis. 2002 Mar; 2(3):190-2.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. Haugo AJ, Watnick PI. Vibrio cholerae CytR is a repressor of biofilm development. Mol Microbiol. 2002 Jul; 45(2):471-83.
  38. 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.
  39. Watnick PI, Kolter R. Steps in the development of a Vibrio cholerae El Tor biofilm. Mol Microbiol. 1999 Nov; 34(3):586-95.
  40. Watnick PI, Chan SI, Dea P. Hydrophobic mismatch in gramicidin A'/lecithin systems. Biochemistry. 1990 Jul 3; 29(26):6215-21.
  41. 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.
  42. 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.
  43. 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.
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