Matthew K. Waldor
Department of Medicine
Brigham and Women's Hospital
Channing Laboratory and HHMI
181 Longwood Avenue
Boston, MA 02115
5 postdoctoral fellows, 3 graduate students, 4 research associates
We are exploring the evolution, pathogenicity, and cell biology of clinically important enteric pathogens including Vibrio cholerae, Vibrio parahaemolyticus and enterohemorrhagic Escherichia coli (EHEC).
Major on-going projects include:
I. Vibrio cholerae chromosome segregation and replication. Using a combination of genetic and biochemical approaches along with fluorescence microscopy, we are exploring the mechanisms that mediate the segregation and replication of the two chromosomes. Homologues of plasmid partitioning (par) genes found on each chromosome appear to mediate the segregation of the two chromosomes in a specific manner. We are defining how these sets of Par proteins mediate V. cholerae chromosome segregation.
II. sRNA control of virulence. Small untranslated RNAs (sRNAs) regulate many cellular processes in non-pathogenic E. coli. Hfq is an RNA binding protein that is important for the activity of many sRNAs. We found that V. cholerae and EHEC lacking Hfq are attenuated in virulence, suggesting that sRNAs, in conjunction with Hfq, control processes that are critical for their pathogenicity. We developed a computer program that enables the rapid identification of putative sRNAs in intergenic regions of bacterial genomes. We are investigating the targets and mechanisms of action of several of the sRNAs that were identified using this software as well as developing deep sequencing approaches to globally characterize bacterial transcriptomes, including sRNAs.
III. Use of infant rabbit models of diarrheal disease to study host-pathogen interactions. Studies of the biology of enteric pathogens during infection have been hampered by the lack of non-surgical small animal models of diarrheal disease. We found that infant rabbits orally inoculated with EHEC or V. cholerae develop severe diarrheal diseases that mimic human infections. We are taking advantage of these models to gain insights into bacterial physiology during growth in the host as well as host-pathogen interactions.
IV. D-amino acids in bacterial physiology. We found that diverse bacteria release a variety of D-amino acids. We are studying the mechanisms by which released D-amino acids control cell wall metabolism and cell shape.
- Rui H, Ritchie JM, Bronson RT, Mekalanos JJ, Zhang Y, Waldor MK. Reactogenicity of live-attenuated Vibrio cholerae vaccines is dependent on flagellins. Proc Natl Acad Sci USA. 107: 4359-64, 2010.
- Yamaichi Y, Duigou S, Shakhnovich EA, Waldor MK. Targeting the replication initiator of the second vibrio chromosome: towards generation of Vibrionaceae-specific antimicrobial agents PloS Pathog. 5:e1000663, 2009.
- Lam H, Oh DC, Cava F, Takas CN, Clardy J, de Pedro MA, Waldor MK. D-amino acids govern stationary phase cell wall remodeling in bacteria. Science 325:1552-5, 2009.
- Shakhnovich EA, Davis BM, Waldor MK. Hfq negatively regulates type III secretion in EHEC and several other pathogens. Mol Microbiol. 74:347-63, 2009.
For a complete listing of publications on PubMed, click here.
BBS webpage updated 5/11/2010