Elucidating the Mechanisms of Action of Antimicrobial Agents

Hudson, Margaret A.; Lockless, Steve W.

doi:10.1128/mbio.02240-21

Cited by 24 publications

(19 citation statements)

References 52 publications

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“…Extensive use and misuse of antibiotics in human and veterinary medicine have escalated the challenge of emergent circulating multidrug-resistant bacterial strains [1][2][3]. Thus, identifying new antimicrobial agents with different mechanisms of action is highly required [4][5][6][7][8][9][10][11]. On the contrary, natural alternatives have a much better image.…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Antibacterial Conglutinins from Lupine Seeds

et al. 2022

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The main target of this work is to discover new protein fractions from natural resources with high antibacterial action. The 7S and 11S globulin fractions, as well as the basic subunit (BS), were isolated from lupine seeds (Lupinus termis), chemically characterized, and screened for antibacterial activity against seven pathogenic bacteria. SDS-PAGE revealed molecular weights ranging from 55 to 75 kDa for 7S globulin, 20–37 kD for 11S globulin, and 20 kD for the BS. 11S globulin and the BS migrated faster on Urea-PAGE toward the cathode compared to 7S globulin. FTIR and NMR showed different spectral patterns between the 7S and 11S globulins but similar ones between 11S globulin and the BS. The MICs of the BS were in the range of 0.05–2 μg/mL against Listeria monocytogenes, Klebsiella oxytoca, Proteus mirabilis, Staphylococcus aureus, Listeria ivanovii, Salmonella typhimurium, and Pseudomonas aeruginosa compared to higher values for 11S globulin. The BS surpassed 11S globulin in antibacterial action, while 7S globulin showed no effect. The MICs of 11S globulin and the BS represented only 5% and 2.5% of the specific antibiotic against L. monocytogenes, respectively. Scanning electron microscopy (SEM) demonstrated different signs of cellular deformation and decay in the protein-treated bacteria, probably due to interaction with the bacterial cell wall and membranes. 11S globulin and the BS can be nominated as effective food biopreservatives.

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Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Antibacterial Conglutinins from Lupine Seeds

et al. 2022

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“…In secondary screening, mostly target-based assays are applied—these allow for the exploration the mode of action. In the past, traditional targets, such as cell wall compartments, DNA, RNA, ribosomes, metabolic enzymes and other proteins, were utilized in screening assays [ 208 , 209 , 210 , 211 ]. In contrast to the primary screening assays, the secondary screens usually involve additional molecular steps (e.g., cloning, generation of mutants, protein purification) and the respective equipment for conducting the measurements.…”

Section: Discussionmentioning

confidence: 99%

“…As there are still compounds with uncharacterized MOA [ 211 ] or antibiotics where the direct physical interactions with the target (e.g., ribosome) are largely unexplored [ 145 ] (e.g., AZ7), the optimization and development of new assays, including novel targets that can be used as tools in antibiotic development and approval, are essential [ 212 , 213 , 214 ]. Furthermore, it is expected that new compounds with unknown MOA will be isolated from natural sources in the future.…”

Section: Discussionmentioning

confidence: 99%

Overview on Strategies and Assays for Antibiotic Discovery

2022

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The increase in antibiotic resistance poses a major threat to global health. Actinomycetes, the Gram-positive bacteria of the order Actinomycetales, are fertile producers of bioactive secondary metabolites, including antibiotics. Nearly two-thirds of antibiotics that are used for the treatment of bacterial infections were originally isolated from actinomycetes strains belonging to the genus Streptomyces. This emphasizes the importance of actinomycetes in antibiotic discovery. However, the identification of a new antimicrobial compound and the exploration of its mode of action are very challenging tasks. Therefore, different approaches that enable the “detection” of an antibiotic and the characterization of the mechanisms leading to the biological activity are indispensable. Beyond bioinformatics tools facilitating the identification of biosynthetic gene clusters (BGCs), whole cell-screenings—in which cells are exposed to actinomycete-derived compounds—are a common strategy applied at the very early stage in antibiotic drug development. More recently, target-based approaches have been established. In this case, the drug candidates were tested for interactions with usually validated targets. This review focuses on the bioactivity-based screening methods and provides the readers with an overview on the most relevant assays for the identification of antibiotic activity and investigation of mechanisms of action. Moreover, the article includes examples of the successful application of these methods and suggestions for improvement.

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“…Determining a specific antimicrobial mechanism of action is often difficult and requires specialized equipment. Common methods for the mechanism of action include affinity chromatography, resistance selection, and screening, and more recently theorized is thermal proteome profiling and bacterial cytological profiling . Affinity chromatography, where direct interactions can be identified, requires large amounts of target proteins.…”

Section: Antimicrobial Agents and Mechanismsmentioning

confidence: 99%

Advances in Nonfouling and Antimicrobial Coatings: Perspectives for the Food Industry

Rudlong

Koga

Goddard

2022

ACS Food Sci. Technol.

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Microbial cross-contamination represents a significant burden to public health and food wasted due to microbial spoilage. Despite established protocols for cleaning and sanitizing surfaces and advances in antimicrobial and nonfouling coatings research, the persistence of pathogenic and spoilage microorganisms remains a challenge in food manufacturing. Specifically, the design and application of antimicrobial and nonfouling coatings in nonfood contact regions of food manufacturing facilities remain an area of research need as these regions are known microbial growth niches. In this review, we survey the state-of-the-art antimicrobial and nonfouling technologies compatible with polyurethane and epoxy coatings suitable for Zone 2/3 regions, such as drain ditches and equipment framework. The properties of polyurethane and epoxy coatings are discussed, followed by a detailed survey of antimicrobial and nonfouling compounds suitable for incorporation into polyurethane and epoxy polymerization chemistries. Challenges and opportunities in the application of antimicrobial and nonfouling coatings to Zones 2/3 are discussed, with an emphasis placed on the design of effective application studies.

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Elucidating the Mechanisms of Action of Antimicrobial Agents

Cited by 24 publications

References 52 publications

Isolation and Characterization of Antibacterial Conglutinins from Lupine Seeds

Isolation and Characterization of Antibacterial Conglutinins from Lupine Seeds

Overview on Strategies and Assays for Antibiotic Discovery

Advances in Nonfouling and Antimicrobial Coatings: Perspectives for the Food Industry

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