BBS Faculty Member - Paula Watnick

Paula Watnick

Division of Infectious Diseases


Boston Children's Hospital
Enders 760
300 Longwood Ave
Boston, MA 02115
Tel: 617-919-2918
Fax: 617-730-0254
Email: paula.watnick@childrens.harvard.edu



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.



Last Update: 8/12/2015



Publications

For a complete listing of publications click here.

 


 

Intestinal pathogens and host metabolism
Houot L. Chang S. Absalon C, Watnick PI, Vibrio cholerae PTS control of carbohydrate transport, biofilm formation, and colonization of the germ-free mouse intestine, Infect Immun, 2010; 78:1482-94.

Wang Z, Hang S, Purdy AE, Watnick PI, Mutations in the IMD pathway and Mustard counter
Vibrio cholerae suppression of intestinal stem cell division, MBio, 2013, 4: e00337-13.

Guichard A, Cruz Moreno B, 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 exocyst-mediated trafficking to intestinal cell junctions, Cell Host and Microbe, 2013, 14:294-305.

Hang S, Purdy AE, Robins WP, Wang Z, Mandal M, Chang S, Mekalanos JJ, and Watnick PI, The acetate switch of an intestinal pathogen disrupts host insulin signaling and lipid metabolism, Cell Host & Microbe, 2014, 16: 592-604.

Vaccine platform
Absalon C, Van Dellen K, and Watnick PI, A communal adhesion mediates attachment of Vibrio cholerae to surfaces, PLoS Pathogens, 2011; 7:e1002210.

Absalon C, Ymele-Leki P, Watnick PI, The biofilm matrix as a platform for protein delivery, MBio, 2012; 4: e00127-2.

Smith DL, Maestre-Reyna M, etc In situ proteolysis of the
Vibrio cholerae matrix protein RbmA promotes biofilm recruitment, Proc Natl Acad Sci, 2015.

Novel antimicrobials from natural products
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: e31307.



© 2015 by the President and Fellows of Harvard College