The Effects of Amixicile, A Pyruvate Ferredoxin Oxidoreductase Inhibitor, on Oral Treponemes

Author

Lucas A. Reed, reedla2Follow

DOI

https://doi.org/10.25772/ZYAZ-H808

Defense Date

2016

Document Type

Thesis

Degree Name

Master of Science

Department

Microbiology & Immunology

First Advisor

Dr. Richard Marconi (PhD)

Second Advisor

Dr. Todd Kitten (PhD)

Third Advisor

Dr. Ping Xu (PhD)

Abstract

Periodontal disease (PD) is a polymicrobial infection characterized by inflammation of the gingiva, alveolar bone resorption, and tooth loss (edentulism). Treponema denticola along with Porphyromonas gingivalis and Tannerella forsythia are among the “Red Complex” and are main etiological agents in PD. Treponemes are a member of the Spirochaeta phylum and are obligate anaerobes, that express pyruvate ferredoxin oxidoreductase (PFOR). The enzyme catalyzes the oxidation of pyruvate to acetyl-CoA and reduced ferredoxin. Amixicile is a novel bacteriostatic derivative of nitazoxanide and an inhibitor of PFOR. In light of the fact that Treponemes express PFOR, this study was conducted to investigate the susceptibility of oral Treponemes to AMX. All oral Treponemes tested were susceptible to AMX and the MIC values were determined ranging of 1.5-4.5 μg mL^-1 for an initial starting cell concentration of 1.9x10⁶ cells mL^-1. Other potentially therapeutic effects for AMX for T. denticola were investigated: motility, hydrogen sulfide production, and serum sensitivity. AMX reduced overall spirochete motility by 50% at sub-MIC concentrations. There was a dose dependent decrease in H₂S production in T. denticola at sub-MIC and MIC values. Furthermore, prior exposure of AMX led to increases in serum sensitivity. Taking into account the fact that other periodontal red complex bacteria express PFOR, AMX could serve as a new selective adjunctive treatment for periodontal disease.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-12-2016