Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

n/a

Abstract Title:

Tomatidine, a lead antibiotic molecule that targetsATP synthase subunit C.

Abstract Source:

Antimicrob Agents Chemother. 2018 Apr 2. Epub 2018 Apr 2. PMID: 29610201

Abstract Author(s):

Maxime Lamontagne Boulet, Charles Isabelle, Isabelle Guay, Eric Brouillette, Jean-Philippe Langlois, Pierre-Étienne Jacques, Sébastien Rodrigue, Ryszard Brzezinski, Pascale B Beauregard, Kamal Bouarab, Kumaraswamy Boyapelly, Pierre-Luc Boudreault, Éric Marsault, François Malouin

Article Affiliation:

Maxime Lamontagne Boulet

Abstract:

Methicillin-resistant(MRSA) is a leading cause of deadly hospital-acquired infections. The discovery of anti-antibiotics and new classes of drugs not susceptible to the mechanisms of resistance shared among bacteria is imperative. We recently showed that tomatidine (TO), a steroidal alkaloid from solanaceous plants, possesses potent antibacterial activity againstsmall colony variants (SCVs), the notoriously persistent form of this bacterium that has been associated with recurrence of infections. Here, using genomic analysis of-generated TO-resistantstrains to identify mutations in genes involved in resistance, we identified the bacterial ATP synthase as the cellular target. Sequence alignments were performed to highlight the modified sequences and the structural consequences of the mutations were evaluated in structural models. Overexpression of thegene inSCVs or introducing the mutation found in thegene of one of the high-level TO-resistantmutant into thegene provided resistance to TO and further validated the identity of the cellular target. FC04-100, a TO derivative which also possesses activity against non-SCV strains, prevents high-level resistance development in prototypic strains and limits the level of resistance observed in SCVs. An ATP synthesis assay allowed the observation of a correlation between antibiotic potency and ATP synthase inhibition. The selectivity index (inhibition of ATP production by mitochondriabacterial ATP synthase) is estimated to be>10-fold for FC04-100.

Study Type : In Vitro Study

Print Options


Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2019 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.