A long-term goal of this research is to understand the molecular mechanisms by which Sinorhizobium meliloti invades the nodules that it elicits on its plant hosts and establishes a productive symbiosis. Another long-term goal is to use knowledge gained from this research to increase our understanding of other bacterial-host interactions, particularly those involving chronic infections of mammals by bacterial pathogens. We have already shown that the synthesis of any of three different S. meliloti extracellular polysaccharides (succinoglycan, EPS II, and K antigen) in a symbiotically active low molecular weight form is required for invasion through infection threads. We will further characterize the quorum sensing regulation of these exopolysaccharides, examine the regulatory role of ExoS-ChvI, and further analyze their biosynthetic mechanisms. We will carry out studies of how the symbiotically active forms of the exopolysaccharide interact with the plant and will test how alteration of the chemical structure, non-carbohydrate modification, and molecular weight distribution of exopolysaccharide influence the architecture of biofilms. We have shown that S. meliloti, a plant symbiont, and Brucella abortus, an animal pathogen, both require the function of the bacA gene for the chronic intracellular infections they cause in their respective hosts. The proposed research will determine the molecular basis of bacA function, test the importance of bacA in other chronic host-pathogen interactions, and further explore possible commonalities between S. meliloti symbiosis and B. abortus pathogenesis. By taking advantage of the recent sequencing of the S. meliloti genome, we have identified 30 genes previously unrecognized as being important for symbiosis and will further study the roles of the most interesting of these. Our work demonstrating the importance of BacA protein in Brucella chronic infections has identified it as a possible target for new classes of drugs active against chronic infections. There is no human vaccine for Brucella, a potential bioterrorism threat, and B. abortus bacA mutants are potential vaccines. Our work will continue to offer insights into how specific low molecular weight oligosaccharides can serve as signals to eukaryotic hosts.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM031030-21
Application #
6541338
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Anderson, James J
Project Start
1982-07-01
Project End
2006-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
21
Fiscal Year
2002
Total Cost
$407,500
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Ghosal, Anubrata; Babu, Vignesh M P; Walker, Graham C (2018) Elevated Levels of Era GTPase Improve Growth, 16S rRNA Processing, and 70S Ribosome Assembly of Escherichia coli Lacking Highly Conserved Multifunctional YbeY Endoribonuclease. J Bacteriol 200:
Budnick, James A; Sheehan, Lauren M; Colquhoun, Jennifer M et al. (2018) Endoribonuclease YbeY Is Linked to Proper Cellular Morphology and Virulence in Brucella abortus. J Bacteriol 200:
Arnold, Markus F F; Shabab, Mohammed; Penterman, Jon et al. (2017) Genome-Wide Sensitivity Analysis of the Microsymbiont Sinorhizobium meliloti to Symbiotically Important, Defensin-Like Host Peptides. MBio 8:
Ghosal, Anubrata; Köhrer, Caroline; Babu, Vignesh M P et al. (2017) C21orf57 is a human homologue of bacterial YbeY proteins. Biochem Biophys Res Commun 484:612-617
Shabab, Mohammed; Arnold, Markus F F; Penterman, Jon et al. (2016) Disulfide cross-linking influences symbiotic activities of nodule peptide NCR247. Proc Natl Acad Sci U S A 113:10157-62
Vercruysse, Maarten; Köhrer, Caroline; Shen, Yang et al. (2016) Identification of YbeY-Protein Interactions Involved in 16S rRNA Maturation and Stress Regulation in Escherichia coli. MBio 7:
Pini, Francesco; De Nisco, Nicole J; Ferri, Lorenzo et al. (2015) Cell Cycle Control by the Master Regulator CtrA in Sinorhizobium meliloti. PLoS Genet 11:e1005232
Price, Paul A; Tanner, Houston R; Dillon, Brett A et al. (2015) Rhizobial peptidase HrrP cleaves host-encoded signaling peptides and mediates symbiotic compatibility. Proc Natl Acad Sci U S A 112:15244-9
De Nisco, Nicole J; Abo, Ryan P; Wu, C Max et al. (2014) Global analysis of cell cycle gene expression of the legume symbiont Sinorhizobium meliloti. Proc Natl Acad Sci U S A 111:3217-24
Penterman, Jon; Abo, Ryan P; De Nisco, Nicole J et al. (2014) Host plant peptides elicit a transcriptional response to control the Sinorhizobium meliloti cell cycle during symbiosis. Proc Natl Acad Sci U S A 111:3561-6

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