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Amixicile, A Novel Antimicrobial Agent, And Its Effect On The Salivary And Subgingival Microbiome In Rhesus Macaque Monkeys, Erin E. Block

Theses and Dissertations

Background/Purpose: Periodontitis is an inflammatory disease with a bacterial etiology in a susceptible host. A selective antibiotic with minimal systemic side effects could be a useful adjunct to traditional periodontal therapy. Amixicile is a novel antimicrobial agent that targets pyruvate: ferredoxin oxidoreductase (PFOR), an enzyme that is critical for anaerobic bacterial metabolism and has been found to have little-to-no side-effects in animal models. The aim of this study was to prospectively evaluate the effect of amixicile on clinical periodontal parameters and the composition of the oral microbiome in rhesus macaque monkeys. It was hypothesized that the amixicile would reduce growth …

Il-36g Cytokine Induction In Oral Epithelial Cells Triggered By Treponema Denticola And Their Role In Chronic Periodontitis, Christopher Blake

Theses and Dissertations

Periodontal disease is a polymicrobial disease affecting 10-15% of the population. Periodontal disease affects the quality of life by reducing mastication and potentially causing tooth loss. Periodontal disease is also linked to more severe, systemic diseases such as cardiovascular disease and rheumatoid arthritis. Development of the diseased state occurs when the plaque biofilm shifts from healthy to dysbiotic. The shift to a dysbiotic biome brings with it a shift in bacterial presence, specifically an increase in gram-negative bacteria, such as T. denticola. T. denticola is a gram-negative, anaerobic spirochete whose relationship with oral epithelial cells is poorly understood. Preliminary data …

Amixicile As A Novel Antimicrobial Treatment For Periodontitis: A Pilot Study In The Non-Human Primate, Macaca Mulatta, Denver J. Lyons

Theses and Dissertations

Periodontitis is an inflammatory disease with a bacterial etiology in a susceptible host. Given the bacterial etiology, a selective antimicrobial agent with minimal side effects could be a useful adjunct to traditional therapy. Amixicile is a novel antimicrobial that targets the pyruvate: ferredoxin oxidoreductase (PFOR) which is an enzyme that is critical for anaerobic bacterial metabolism. It has been found to have no effect on commensal, aerobic microbes and has little to no side-effects thus far in animal models. In this study, two nonhuman primates of the Macaca mulatta species with naturally occurring mild chronic periodontitis were studied before and …

Selenomonas Sputigena: Growth Conditions And Projected Virulence Factors Of An Emerging Oral Pathogen, Kayla A. Keller

Theses and Dissertations

Periodontal diseases are ubiquitous diseases. They can affect people through a chronic infection that happens over a lifetime, but also as an aggressive infection that afflicts the younger population. It not only results in tooth loss and a lower quality of life, but it can also lead to fatal secondary infections like cervical cancer, heart disease, and Alzheimer’s disease. This study looks at Selenomonas sputigena, an emerging oral pathogen, that has been hypothesized to contribute to periodontal disease. It has been linked to fatal septicemia and has been found in increased abundance within the oral biofilm during peak infection. …

The Effects Of Amixicile On Sub-Gingival Biofilm Cultured From Humans, Kian Azarnoush

Theses and Dissertations

Periodontitis is an inflammatory disease of the oral cavity induced by anaerobic bacteria, that remains to be the primary cause of tooth loss in adults worldwide. Finding an anti-microbial therapeutic to selectively target periodontal pathogens has proven to be difficult, and current treatment modalities only provide a transient benefit. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate, a critical step in metabolism. Our study aimed to evaluate the efficacy of amixicile in inhibiting the growth of bacteria harvested …

Amixicile Inhibits Anaerobic Bacteria Within An Oral Microbiome Derived From Patients With Chronic Periodontitis, Kane Ramsey

Theses and Dissertations

Periodontitis is a chronic inflammatory disease caused by pathogenic bacteria residing in a complex biofilm within a susceptible host. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate. Our study aimed to evaluate the efficacy of amixicile, when compared to metronidazole, in inhibiting the growth of bacteria present in a microbiome harvested from patients with chronic periodontitis.

Plaque samples were harvested from patients with severe chronic periodontitis and cultured under anaerobic conditions. The microbiomes were grown in the presence …

Defining The Bacterial Flora Of Periodontal Pockets In Chronic Periodontitis Patients, Rafael Rodriguez

Theses and Dissertations

PURPOSE: The purpose of this study is to describe the subgingival bacterial biodiversity in untreated chronic periodontitis patients through the use of next generation 16S rRNA molecular analysis, and to determine similarities or differences between deep and shallow pockets within the same patients. METHODS: The analysis involved paired subgingival plaque samples from 24 subjects diagnosed with Generalized Moderate to Severe Chronic Periodontitis. One sample was selected from a single site having a probing depth >5 mm (i.e. Deep Site), and the other from a site with a probing depth <3mm (i.e. Shallow Site) within each subject. Bacterial DNA amplification of the V4-V6 region of the 16S rRNA was performed. The amplicons were sequenced via 454 Roche Genome Sequencer FLX System. The identified sequences were evaluated, and then compared to calculated false discovery rates. RESULTS: A total of 119 independent microbial genera were identified within the samples analyzed. Seven genera were identified to be statistically significant (p<0.05) in their association to deep or shallow sites following t-test and boot strap randomization: Actinomyces (p=0.004), Methylobacterium (p=0.028), Veillonella (p=0.028), and Rothia (p=0.038), and Streptococcus (p=0.033) in Shallow sites; while Mycoplasma (p=0.007) and Fusobacterium (p=0.016) were associated with deep sites. However, taking into account the calculated false discovery rates, it is suggested that none of the 119 microbial genera identified in this study were significantly associated with either deep nor shallow sites. CONCLUSION: The microbial genera identified within this study to be associated with deep and shallow sites follows the traditional pattern anticipated from the literature. However, the calculated false discovery rates suggest that these results may have occurred by chance and not due to a true difference.

The Effect Of Single Nucleotide Polymorphisms (Snps) In Toll-Like Receptors -2, -4, -9, And Cd14 Genes In An African-American Population With Chronic Periodontitis, Willard Maughan

Theses and Dissertations

AIM: to determine if a relationship exists between TLR-2, TLR-4, TLR-9, or CD14 polymorphisms and risk for developing chronic periodontal disease in an African-American population. This is the first study conducted to determine role of SNPs in TLR genes and CD14 gene in a periodontally-diseased African-American population. Additionally, this is the first study to assess the role of TLR-9 polymorphism in periodontitis patients. METHODS: A total of 130 subjects were involved in the study. The chronic periodontitis (CP) group contained 73 subjects, and the healthy control (NP) group 57subjects. Genotyping was performed in TLR2 (G2408A), TLR4 (A896G),TLR9 (T1486C) and CD14 …

Serum Anti-Phosphorylcholine And Anti-Cardiolipin Concentrations Following Periodontal Scaling And Root Planing, Reve W. Chaston

Theses and Dissertations

Atherosclerosis is an insidious disease with serious morbidity and mortality including ischemic heart disease, stroke, and myocardial infarction. This condition is progressive and can start early in life eventually leading to large plaques and arterial occlusion. Two key components of this process are the immune system and lipids; in particular, LDL which accumulates within the arterial walls and macrophages which recognize and engulf oxidized-LDL (oxLDL) to form foam cells. Knowing that certain antibodies directed against bacterial antigens such as phosphorylcholine (PC) and cardiolipin (CL) show opsonizing cross-reactivity with oxLDL it can be proposed that there is a link between immune …