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SC3: Regulation of polar adhesion during Sinorhizobium meliloti infection

SC3：苜蓿中华根瘤菌感染期间极性粘附的调节

基本信息

批准号：
9073175
负责人：
Joseph Chiung-Chu Chen
金额：
$ 10.2万
依托单位：
SAN FRANCISCO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9073175
关键词：
Adhesions Adhesives Alleles Alphaproteobacteria Antibiotics Antimicrobial Resistance Area Bacteria Bacterial Adhesins Bacterial Adhesion Bacterial Infections Brucella Brucella abortus Bypass Cations Cell Cycle Cell Polarity Cells Communicable Diseases Communities Cues Culture Media Disease Environment Environmental Risk Factor Exposure to Extracellular Matrix Exudate Fabaceae Foundations Funding Future Gene Expression Genes Genetic Glean Goals Grant Growth Host Defense In Vitro Individual Infection Intervention Investigation Knowledge Laboratories Lead Left Length Link Location Mammalian Cell Melilotus Methods Microbial Biofilms Microscopy Modeling Molecular Mutation Nitrogen Nutrient Organelles Organism Orthologous Gene Pathogenesis Pathway interactions Pattern Peptones Phenotype Physiological Plant Roots Plants Play Point Mutation Polymers Prevalence Prevention Production Productivity Property Proteins Proteobacteria Public Health Regulation Research Research Personnel Rickettsia Role Sinorhizobium meliloti Site Students Sum Surface Symbiosis Tissues Tube Work antimicrobial antimicrobial drug bacterial resistance career cell motility combat commensal microbes design experience fitness human disease improved inorganic phosphate microbial mutant novel pathogen prevent public health relevance tissue fixing

项目摘要

DESCRIPTION (provided by applicant): The proposed project will decipher the molecular mechanisms that control adhesin production and biofilm formation in alpha-proteobacteria, a physiologically heterogeneous group that includes a number of pathogens that cause serious human diseases. Biofilm formation plays a crucial role in the survival of bacteria in diverse environments and is of great relevance to public health. Cells in biofilms attach recalcitrantly to biotic and abiotic surfaces, develop increased resistance to antimicrobial agents, and contribute to persistent infections. Although limiting biofilm formation has the potential to prevent and restrict bacterial infections, little is known about biofilm formation by alpha-proteobacteria and how it facilitates host colonization. Recently, we discovered a mutation in the conserved cell polarity factor PodJ in domesticated, laboratory strains of Sinorhizobium meliloti -- a model alpha-proteobacterium that establishes mutualistic symbioses with compatible legumes by colonizing their root tissues and fixing molecular nitrogen in exchange for nutrients from host plants. Correcting the mutation and restoring the PodJ polarity factor to the version found in environmental isolates of S. meliloti enabled the Rm1021 laboratory strain to produce a polar adhesin, called holdfast, and to develop robust biofilms. Furthermore, the corrected allele (podJ+) conferred a competitive advantage during symbiosis. These novel phenotypes have never been characterized because commonly used S. meliloti strains all possess the mutation. The goal of this proposal is to elucidate the genetic circuitry that links the cell cycle-dependent polarity factor PodJ to the regulated production of adhesive holdfast, which promotes biofilm formation and enhances fitness, particularly during host colonization. Achieving this goal involves accomplishing the following four specific aims: (1) determine the subcellular locations of PodJ and holdfast as a function of the cell cycle; (2) evaluate environmental conditions for their effects on holdfast synthesis and biofilm formation; (3) assess if holdfast increases attachment to host tissue; and (4) identify and define the roles of cellular factors that participae in holdfast production. Results from the investigation will provide a better model of how conserved and species-specific pathways can contribute to adhesion and biofilm formation in alpha-proteobacteria. Such knowledge will provide the foundation for developing new methods to combat biofilms and bacterial infections. In addition to accomplishing the scientific objectives described above, funding of this proposal will enhance the research productivity and grant competitiveness of the investigator and allow students, particularly those from underrepresented backgrounds, to gain exposure to an exciting area of research, thus nurturing their pursuits of biomedical careers.