ArticlePloS one2010
A new approach for the discovery of antibiotics by targeting non-multiplying bacteria: a novel topical antibiotic for staphylococcal infections.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 81 citations in OpenAlex.
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- Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique.Marine drugs · 2021Article
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- Impetigo Animal Models: A Review of Their Feasibility and Clinical Utility for Therapeutic Appraisal of Investigational Drug Candidates.Antibiotics (Basel, Switzerland) · 2020Review
- A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery.Antibiotics (Basel, Switzerland) · 2020Article
- Antimicrobial Activity of the Quinoline Derivative HT61 against Staphylococcus aureus Biofilms.Antimicrobial agents and chemotherapy · 2020Article
- Facile One Pot Greener Synthesis of Sophorolipid Capped Gold Nanoparticles and its Antimicrobial Activity having Special Efficacy Against Gram Negative Vibrio cholerae.Scientific reports · 2020Article
- Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-ResistantFrontiers in microbiology · 2019Article
- A Novel Delivery System for the Controlled Release~of Antimicrobial Peptides: Citropin 1.1 and Temporin A.Polymers · 2018Article
- Strategies against methicillin-resistant Staphylococcus aureus persisters.Future medicinal chemistry · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In a clinical infection, multiplying and non-multiplying bacteria co-exist. Antibiotics kill multiplying bacteria, but they are very inefficient at killing non-multipliers which leads to slow or partial death of the total target population of microbes in an infected tissue. This prolongs the duration of therapy, increases the emergence of resistance and so contributes to the short life span of antibiotics after they reach the market. Targeting non-multiplying bacteria from the onset of an antibiotic development program is a new concept. This paper describes the proof of principle for this concept, which has resulted in the development of the first antibiotic using this approach. The antibiotic, called HT61, is a small quinolone-derived compound with a molecular mass of about 400 Daltons, and is active against non-multiplying bacteria, including methicillin sensitive and resistant, as well as Panton-Valentine leukocidin-carrying Staphylococcus aureus. It also kills mupirocin resistant MRSA. The mechanism of action of the drug is depolarisation of the cell membrane and destruction of the cell wall. The speed of kill is within two hours. In comparison to the conventional antibiotics, HT61 kills non-multiplying cells more effectively, 6 logs versus less than one log for major marketed antibiotics. HT61 kills methicillin sensitive and resistant S. aureus in the murine skin bacterial colonization and infection models. No resistant phenotype was produced during 50 serial cultures over a one year period. The antibiotic caused no adverse affects after application to the skin of minipigs. Targeting non-multiplying bacteria using this method should be able to yield many new classes of antibiotic. These antibiotics may be able to reduce the rate of emergence of resistance, shorten the duration of therapy, and reduce relapse rates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.