Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy

Periodontitis is an inflammatory condition triggered by selected oral microbiota; thus treatment strategies should be aimed at reducing the abundance of the pathogenic bacteria. An obstacle to preclinical testing of such strategies is the availability of reliable animal models. Here, a non-human pri...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Qin Gui, Denver J. Lyons, Janina Golob Deeb, B. Ross Belvin, Paul S. Hoffman, Janina P. Lewis
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	amixicile anaerobic bacteria microbiome periodontitis non-human primates (NHP) targeted antibiotic Dentistry RK1-715
Acceso en línea:	https://doaj.org/article/39c56e52976f459d9e79ad73eca120a3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:39c56e52976f459d9e79ad73eca120a3
record_format	dspace
spelling	oai:doaj.org-article:39c56e52976f459d9e79ad73eca120a32021-11-05T05:54:32ZNon-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy2673-484210.3389/froh.2021.752929https://doaj.org/article/39c56e52976f459d9e79ad73eca120a32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/froh.2021.752929/fullhttps://doaj.org/toc/2673-4842Periodontitis is an inflammatory condition triggered by selected oral microbiota; thus treatment strategies should be aimed at reducing the abundance of the pathogenic bacteria. An obstacle to preclinical testing of such strategies is the availability of reliable animal models. Here, a non-human primate (NHP), Macaca mulatta, was used to examine the effectiveness of a novel antimicrobial, amixicile, which inhibits pyruvate–ferredoxin oxidoreductase (PFOR) present in anaerobic bacteria. Animals were assessed for their periodontal health, including radiography, clinical attachment loss (CAL), presence of plaque (PI), bleeding on probing (BOP) and pocket depth (PD), and sampled for saliva, gingival crevicular fluid (GCF), and subgingival plaque to determine their baseline clinical status. Amixicile was then administered for 2 weeks (40 mg/kg/day) and the animals were monitored for periodontal health immediately after the antibiotic treatment, then at 1 month-, 3 months-, and 6-months posttreatment. Microbial species present in plaque and saliva were determined through 16S rDNA sequencing. Baseline assessment of the microbiome has shown a significant proportion of bacteria belonging to the Streptococcus, Haemophilus, Porphyromonas, Gemella, and Fusobacterium genera. The abundance of Porphyromonas and Fusobacterium was reduced following treatment with amixicile, whereas that of Escherichia, Haemophilus, and Gemella were elevated. CAL, PD, and BOP were also significantly reduced following the treatment. In conclusion, the NHP model proves useful for preclinical studies of strategies targeting selected members of the oral microbiome. We show that amixicile reduces the levels of anaerobic bacteria under in vivo conditions, correlating with a reduction in CAL, PD, and BOP, thus validating its usefulness as an antimicrobial strategy.Qin GuiDenver J. LyonsDenver J. LyonsJanina Golob DeebB. Ross BelvinPaul S. HoffmanJanina P. LewisJanina P. LewisJanina P. LewisFrontiers Media S.A.articleamixicileanaerobic bacteriamicrobiomeperiodontitisnon-human primates (NHP)targeted antibioticDentistryRK1-715ENFrontiers in Oral Health, Vol 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amixicile anaerobic bacteria microbiome periodontitis non-human primates (NHP) targeted antibiotic Dentistry RK1-715
spellingShingle	amixicile anaerobic bacteria microbiome periodontitis non-human primates (NHP) targeted antibiotic Dentistry RK1-715 Qin Gui Denver J. Lyons Denver J. Lyons Janina Golob Deeb B. Ross Belvin Paul S. Hoffman Janina P. Lewis Janina P. Lewis Janina P. Lewis Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy
description	Periodontitis is an inflammatory condition triggered by selected oral microbiota; thus treatment strategies should be aimed at reducing the abundance of the pathogenic bacteria. An obstacle to preclinical testing of such strategies is the availability of reliable animal models. Here, a non-human primate (NHP), Macaca mulatta, was used to examine the effectiveness of a novel antimicrobial, amixicile, which inhibits pyruvate–ferredoxin oxidoreductase (PFOR) present in anaerobic bacteria. Animals were assessed for their periodontal health, including radiography, clinical attachment loss (CAL), presence of plaque (PI), bleeding on probing (BOP) and pocket depth (PD), and sampled for saliva, gingival crevicular fluid (GCF), and subgingival plaque to determine their baseline clinical status. Amixicile was then administered for 2 weeks (40 mg/kg/day) and the animals were monitored for periodontal health immediately after the antibiotic treatment, then at 1 month-, 3 months-, and 6-months posttreatment. Microbial species present in plaque and saliva were determined through 16S rDNA sequencing. Baseline assessment of the microbiome has shown a significant proportion of bacteria belonging to the Streptococcus, Haemophilus, Porphyromonas, Gemella, and Fusobacterium genera. The abundance of Porphyromonas and Fusobacterium was reduced following treatment with amixicile, whereas that of Escherichia, Haemophilus, and Gemella were elevated. CAL, PD, and BOP were also significantly reduced following the treatment. In conclusion, the NHP model proves useful for preclinical studies of strategies targeting selected members of the oral microbiome. We show that amixicile reduces the levels of anaerobic bacteria under in vivo conditions, correlating with a reduction in CAL, PD, and BOP, thus validating its usefulness as an antimicrobial strategy.
format	article
author	Qin Gui Denver J. Lyons Denver J. Lyons Janina Golob Deeb B. Ross Belvin Paul S. Hoffman Janina P. Lewis Janina P. Lewis Janina P. Lewis
author_facet	Qin Gui Denver J. Lyons Denver J. Lyons Janina Golob Deeb B. Ross Belvin Paul S. Hoffman Janina P. Lewis Janina P. Lewis Janina P. Lewis
author_sort	Qin Gui
title	Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy
title_short	Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy
title_full	Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy
title_fullStr	Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy
title_full_unstemmed	Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy
title_sort	non-human primate macaca mulatta as an animal model for testing efficacy of amixicile as a targeted anti-periodontitis therapy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/39c56e52976f459d9e79ad73eca120a3
work_keys_str_mv	AT qingui nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy AT denverjlyons nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy AT denverjlyons nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy AT janinagolobdeeb nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy AT brossbelvin nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy AT paulshoffman nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy AT janinaplewis nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy AT janinaplewis nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy AT janinaplewis nonhumanprimatemacacamulattaasananimalmodelfortestingefficacyofamixicileasatargetedantiperiodontitistherapy
_version_	1718444462694203392

Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy

Ejemplares similares