ArticlePloS one2016
Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
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- A small-molecule membrane fluidizer re-sensitizes methicillin-resistantAntimicrobial agents and chemotherapy · 2023Article
- Identification of 5-(Aryl/Heteroaryl)amino-4-quinolones as Potent Membrane-Disrupting Agents to Combat Antibiotic-Resistant Gram-Positive Bacteria.Journal of medicinal chemistry · 2022Article
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- PaP1, a Broad-Spectrum Lysin-Derived Cationic Peptide to Treat Polymicrobial Skin Infections.Frontiers in microbiology · 2022Article
- Using membrane perturbing small molecules to target chronic persistent infections.RSC medicinal chemistry · 2021Review
- Isolation, characterization, and molecular identification of soil bacteria showing antibacterial activity against human pathogenic bacteria.Journal, genetic engineering & biotechnology · 2021Article
- Effect of naturally isolated hydroquinone in disturbing the cell membrane integrity ofHeliyon · 2021Article
- A Cell-Free Screen for Bacterial Membrane Disruptors Identifies Mefloquine as a Novel Antibiotic Adjuvant.Antibiotics (Basel, Switzerland) · 2021Article
- Evaluating the Antibacterial Activity and Mode of Action of Thymol-Loaded Chitosan Nanoparticles Against Plant Bacterial PathogenFrontiers in microbiology · 2021Article
- Comparison of Proteomic Responses as Global Approach to Antibiotic Mechanism of Action Elucidation.Antimicrobial agents and chemotherapy · 2020Article
- The Antistaphylococcal Lysin, CF-301, Activates Key Host Factors in Human Blood To Potentiate Methicillin-ResistantAntimicrobial agents and chemotherapy · 2019Article
- Potential of Biocellulose Carrier Impregnated with Essential Oils to Fight Against Biofilms Formed on Hydroxyapatite.Scientific reports · 2019Article
- Antimicrobial and anti-biofilm activity of hexadentated macrocyclic complex of copper (II) derived from thiosemicarbazide against Staphylococcus aureus.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies.
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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.