Regulatory Mechanisms Controlling Expression of P. gingivalis Surface Structures

控制牙龈卟啉单胞菌表面结构表达的调控机制

• 批准号: 9986131
• 负责人: Mary Ellen Davey
• 金额: $ 38.13万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9986131
• 关键词: Adult; Anaerobic Bacteria; Antigens; Antisense RNA; Bacteria; Biochemical; Cardiovascular Diseases; Cell surface; Cellular Metabolic Process; ChIP-seq; Chromosomes; Chronic; Communities; DNA; Development; Diabetes Mellitus; Disease; Disease Progression; Disease model; EMSA; Elements; Etiology; Family member; Gene Expression; Genes; Genetic; Genomics; Goals; Homeostasis; Immune Evasion; Inflammatory; Interferometry; Knock-out; Knowledge; Lead; Link; Lipopolysaccharides; Microbe; Microbial Biofilms; Modeling; Molecular; Mus; Nucleotides; Nutritional; Outcome Study; Pathogenesis; Pathogenicity; Periodontal Diseases; Play; Polysaccharides; Population; Porphyromonas gingivalis; Prevention; Production; Proteins; RNA; Regulation; Regulatory Pathway; Research; Role; Stroke; Structure; Surface; Surface Properties; Systemic disease; Techniques; Testing; Transcript; United States; Virulence; Virulent; capsule; cost; immunoregulation; integrin beta6; member; mouse model; mutant; novel therapeutic intervention; oral anaerobes; oral pathogen; overexpression; pathogen; pathogenic bacteria; programs; public health relevance; response; subgingival biofilm; transcriptome sequencing

 DESCRIPTION (provided by applicant): Porphyromonas gingivalis (Pg) is a Gram-negative anaerobe, strongly implicated in the etiology of adult periodontal disease. This research will increase our understanding of the molecular mechanisms that control synthesis of Pg cell surface glycans, and determine how changes in synthesis relate to biofilm persistence and pathogenicity. Our overarching model is that the biofilm state acts as a reservoir of bacteria, while capsule synthesis is linked to a transition to virulence and disruption of homeostasis. We have discovered that DNABII family members in Pg (HU PG0121 and HU PG1258) are involved in controlling synthesis of this surface polysaccharide. DNABII proteins are members of the Nucleoid Associated Proteins (NAPs), a class of proteins that possess multiple functions in maintaining the structure and function of DNA and RNA and are known to be critical for regulation of cell metabolism, the response to environmental perturbations, and in controlling the transition to and from a quiescent state. We have also identified an antisense RNA encoded in the 5'-end of the capsule locus (PG0104-PG0121) within a large 77bp inverted repeat (77bpIR) element. Deletion or over- expression of the region encoding this asRNA alters the synthesis of both LPS and K-antigen capsule. Our working model is that DNABII proteins interact with this asRNA and control expression of both the sense and antisense transcripts in this region. We have designated the asRNA asSuGR, for antisense Surface Glycan Regulator. The central hypothesis of this project is that HU PG0121 and HU PG1258 are key NAPs that play a fundamental role in modulating Pg pathogenicity. In these studies we will determine how these proteins and the 77bpIR element control synthesis of capsule and LPS. Our overall goal is to identify regulatory pathways that control the switch from a persistent, surface-attached state as a commensal to a virulent state capable of disrupting microbe-host homeostasis. The research proposed in this application is significant because understanding the control of surface property changes is a vital link to understanding the switch this commensal makes to a virulent pathogen. As an outcome of these studies, we will have characterized regulatory mechanisms that control the synthesis of surface glycans, key virulence determinants. This information will lead to a better understanding of the regulatory networks that either direct P. gingivalis to become a virulent pathogen or to continue to lie low and persist. Our results will potentially lead to the development of new therapeutic strategies for modulating biofilm formation by this oral pathogen.



项目成果

Effects of phenol feeding pattern on microbial community structure and cometabolism of trichloroethylene.

苯酚摄食方式对微生物群落结构和三氯乙烯共代谢的影响。

• DOI: 10.1128/aem.62.8.2953-2960.1996
• 发表时间: 1996
• 期刊: Applied and environmental microbiology
• 影响因子: 4.4
• 作者: Shih,C;Davey,ME;Zhou,J;Tiedje,JM;Criddle,CS
• 通讯作者: Criddle,CS

A biochemical analysis of the interaction of Porphyromonas gingivalis HU PG0121 protein with DNA.

• DOI: 10.1371/journal.pone.0093266
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Tjokro NO;Rocco CJ;Priyadarshini R;Davey ME;Goodman SD
• 通讯作者: Goodman SD

A Porphyromonas gingivalis Capsule-Conjugate Vaccine Protects From Experimental Oral Bone Loss.

• DOI: 10.3389/froh.2021.686402
• 发表时间: 2021
• 期刊: Frontiers in oral health
• 作者: Rocha FG;Berges A;Sedra A;Ghods S;Kapoor N;Pill L;Davey ME;Fairman J;Gibson FC 3rd
• 通讯作者: Gibson FC 3rd

Tracking dynamic interactions during plaque formation.

跟踪斑块形成过程中的动态相互作用。

• DOI: 10.1128/jb.01344-08
• 发表时间: 2008
• 期刊: Journal of bacteriology
• 影响因子: 3.2
• 作者: Davey,MaryEllen

Natural antigenic differences in the functionally equivalent extracellular DNABII proteins of bacterial biofilms provide a means for targeted biofilm therapeutics.

• DOI: 10.1111/omi.12157
• 发表时间: 2017-04
• 期刊: Molecular oral microbiology
• 影响因子: 3.7
• 作者: Rocco CJ;Davey ME;Bakaletz LO;Goodman SD
• 通讯作者: Goodman SD