☆ 4.6 Review

Overview on Strategies and Assays for Antibiotic Discovery

PHARMACEUTICALS (2022)

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Review Microbiology

Antibiotic resistance in the environment

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Summary: Antibiotic resistance is a global health challenge, with factors driving evolution and transmission being important to quantify and identify. The environment plays a crucial role, and understanding and managing the resistance crisis can be achieved through implementing monitoring and assessment methods to reduce risks.

NATURE REVIEWS MICROBIOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Purification and characterization of antibacterial surfactin isoforms produced by Bacillus velezensis SK

Sagar S. Barale et al.

Summary: Bacillus velezensis SK, isolated from soil, exhibits broad-spectrum antimicrobial activity. Efficient extraction of antimicrobial compounds produced in different mediums was achieved using Diaion HP-20 resin. The antimicrobial compound, characterized by TLC, FTIR, and in-situ bioautography analysis, was found to be cyclic lipopeptides and was purified using silica gel, size exclusion, dual gradient, and RP-HPLC chromatography techniques. Growth kinetic studies showed that Bacillus velezensis SK produces a mixture of lipopeptides. LC-ESI-MS analysis of partially purified lipopeptide identified surfactin variants, and further analysis revealed the presence of C-15-surfactin homologues. The isolated surfactin exhibited good antimicrobial activity against drug-resistant bacteria.

AMB EXPRESS (2022)

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The cost of resistance

Andrea Du Toit

Summary: This study demonstrates that colistin resistance in Klebsiella pneumoniae leads to a fitness defect in gut colonization, while enhancing bacterial survival outside the host, thus facilitating efficient host-to-host transmission.

NATURE REVIEWS MICROBIOLOGY (2022)

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Review Microbiology

Elucidating the Mechanisms of Action of Antimicrobial Agents

M. Ashley Hudson et al.

Summary: Despite the growing antibiotic resistance crisis, the discovery and approval rate of new antimicrobials has declined rapidly over the past 75 years. Understanding the mechanism(s) of action of newly identified antibiotics is a barrier for their further development. Recent research using profiling methods, such as thermal proteome profiling in bacteria, has provided valuable insights into the mechanisms of discovered antimicrobials. This article provides an overview of the importance of target deconvolution in antimicrobial discovery, discussing both traditional approaches and the latest advances in methodologies for identifying antimicrobial targets.

MBIO (2022)

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Review Food Science & Technology

Overview of Recent Liquid Chromatography Mass Spectrometry-Based Methods for Natural Toxins Detection in Food Products

Annalisa De Girolamo et al.

Summary: This article reviews the relevant literature on liquid chromatography mass spectrometry methods for the analysis of various natural toxins in food. A total of 96 papers from 2011 to 2021 were selected for review. Different approaches in sample preparation, chromatographic separation, and detection mode are discussed. The article particularly focuses on the analytical performance characteristics obtained during the validation process and the application to real samples.

TOXINS (2022)

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Review Chemistry, Medicinal

Targeted Large-Scale Genome Mining and Candidate Prioritization for Natural Product Discovery

Jessie James Limlingan Malit et al.

Summary: Large-scale genome-mining analyses have identified numerous cryptic biosynthetic gene clusters (BGCs) as a valuable source of novel bioactive natural products. Effective strategies and computational methods are essential for selecting appropriate BGCs for further characterization and production of natural products. Studies have successfully produced compounds with high chemical novelty, novel biosynthesis pathways, and potent bioactivities by prioritizing candidate BGCs based on different logics such as detection of resistance genes, phylogenomics analysis, and targeting specific chemical structures.

MARINE DRUGS (2022)

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The past, present, and future of antibiotics

Michael A. Cook et al.

Summary: Antibiotics have played a crucial role in modern medicine, but they are facing challenges of microbial resistance and traditional reimbursement models. Therefore, innovation is needed in policy, quantitative understanding of societal value, and investment in alternatives. Significant investment in research and development is also necessary to address the antibiotic crisis.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance

Dmitry Leshchiner et al.

Summary: Understanding how bacteria evade antibiotics and develop resistance is crucial for the development of novel therapeutics and diagnostics. In this study, the authors conducted a comprehensive genetic analysis of how the human pathogen Streptococcus pneumoniae responds to different antibiotics. They identified genes and cellular processes that contribute to altered drug susceptibility and demonstrated their potential as therapeutic targets.

NATURE COMMUNICATIONS (2022)

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Recent Advances in Histidine Kinase-Targeted Antimicrobial Agents

Hongtong Chen et al.

Summary: The prevalence of antimicrobial-resistant pathogens poses a challenge to clinical practice, necessitating the discovery of new antibacterial drugs. One potential target is the histidine kinase (HK) in the two-component system (TCS) of bacteria. This review highlights the structural basis and functional importance of HKs as a target in the development of novel antimicrobials, and summarizes the latest research progress in small-molecule HK inhibitors as potential antimicrobial drugs.

FRONTIERS IN CHEMISTRY (2022)

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Review Microbiology

Riboflavin as a promising antimicrobial agent? A multi-perspective review

Nuratiqah Farah et al.

Summary: Riboflavin has dual effects as an antimicrobial agent and a host immune modulator, making it a potential candidate for resolving microbial infections and for use in photodynamic therapy against various pathogens and microbial biofilm-associated infections.

CURRENT RESEARCH IN MICROBIAL SCIENCES (2022)

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Review Biochemistry & Molecular Biology

Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents

Ashley King et al.

Summary: Antibiotic resistance is a global concern, requiring novel approaches to treating bacterial infections. Bacterial kinases, explored as new drug targets, hold promise for development into new therapeutic agents against bacterial infections.

CHEMICAL BIOLOGY & DRUG DESIGN (2021)

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Review Chemistry, Medicinal

Amino Acid Based Antimicrobial Agents - Synthesis and Properties

Michal G. Nowak et al.

Summary: The structures of many antibacterial, antifungal, or antiprotozoal agents are based on amino acid scaffolds. The amino acid skeleton is crucial for their antimicrobial activity, particularly in the case of aminophosphonate or aminoboronate analogs. The synthesis of amino acid antimicrobials presents a specific challenge, especially in terms of enantioselective methods.

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Improving target assessment in biomedical research: the GOT-IT recommendations

Christoph H. Emmerich et al.

Summary: Academic research plays a crucial role in identifying new drug targets, and this Perspective introduces a framework to assist academic scientists and funders in prioritizing target assessment activities to achieve scientific goals and objectives related to licensing, industry collaboration, and clinical trials.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Review Biochemistry & Molecular Biology

The periodic table of ribonucleotide reductases

Terry B. Ruskoski et al.

Summary: Transition metal ions are necessary cofactors for RNR enzymes, generating oxidants that initiate catalysis. Different classes of enzymes have unique structures and cofactors, with diverse bioinorganic and radical cofactors found in class I RNRs. Recent research focuses on the discovery, assembly mechanisms, and potential functions of novel radical initiating cofactors in class I RNRs.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Review Infectious Diseases

Riboswitches as Drug Targets for Antibiotics

Vipul Panchal et al.

Summary: Riboswitches, located in the untranslated region of RNA, regulate gene expression and are potential antibacterial targets. Lead compounds against various riboswitches have been identified through different screening methods and structure design.

ANTIBIOTICS-BASEL (2021)

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Article Microbiology

Streptomyces sp. M54: an actinobacteria associated with a neotropical social wasp with high potential for antibiotic production

Bernal Matarrita-Carranza et al.

Summary: Insects symbiotic with Streptomyces have been identified as a promising source for new antibiotics. The genome of Streptomyces sp. M54, associated with the eusocial wasp Polybia plebeja, was found to harbor multiple gene clusters for secondary metabolites and produce antimicrobial compounds active against both natural enemies and human pathogens. Phylogenetic and genomic analyses revealed the relationship of Streptomyces sp. M54 with other host-associated strains, highlighting its potential for novel antibiotic discovery.

ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY (2021)

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Review Biochemistry & Molecular Biology

Recent Progress in Small Molecular Inhibitors of DNA Gyrase

Ruo-Jun Man et al.

Summary: In the past few decades, bacterial resistance has increased due to antibiotic abuse, leading to the discovery of super species of bacteria that threaten human health. Developing novel antibacterial agents to combat drug resistance is urgent. DNA gyrase, an essential enzyme for DNA replication and transcription, is a key target for bacterial inhibitors, with many inhibitors developed in recent years.

CURRENT MEDICINAL CHEMISTRY (2021)

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Development of an agar-plug cultivation system for bioactivity assays of actinomycete strain collections

Nico Ortlieb et al.

Summary: Natural products are valuable for drug development, and actinomycetes have been crucial for antibiotic discovery. This study developed a medium-throughput system for screening actinomycete strain collections in agar-plug assays, making it more convenient to conduct bioactivity assays against monitor strains.

PLOS ONE (2021)

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Review Biotechnology & Applied Microbiology

Natural products in drug discovery: advances and opportunities

Atanas G. Atanasov et al.

Summary: Natural products and their analogues have historically played a significant role in pharmacotherapy, however, they also present challenges. Recent technological and scientific developments are addressing these challenges and revitalizing interest in natural products as drug leads, particularly for combating antimicrobial resistance.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Novel Targets and Mechanisms in Antimicrobial Drug Discovery

Donatella Tondi

ANTIBIOTICS-BASEL (2021)

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Bioactive Natural Products in Actinobacteria Isolated in Rainwater From Storm Clouds Transported by Western Winds in Spain

Aida Sarmiento-Vizcaino et al.

Summary: Actinobacteria, particularly Streptomyces strains, isolated from rain samples collected during various precipitation events in different locations in Spain were found to originate from diverse sources such as the North Atlantic Ocean, the Pacific and Arctic Oceans, and terrestrial sources from North America and Europe. The study also identified rare Actinobacterial genus Nocardiopsis strains in some events. LC-UV-MS analysis of bioactive secondary metabolites revealed a variety of compounds, with a significant percentage exhibiting antibiotic and antitumor properties. The study highlights the atmosphere as a rich source of Actinobacteria producing bioactive natural products with potential implications in medicine and biotechnology.

FRONTIERS IN MICROBIOLOGY (2021)

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Review Chemistry, Multidisciplinary

Currently Available Strategies for Target Identification of Bioactive Natural Products

Gen Li et al.

Summary: This review systematically describes commonly used strategies for target identification of bioactive natural products through the application of probe and non-probe approaches, comparing the merits and demerits of each method with recent examples in order to select the optimal techniques for target identification.

FRONTIERS IN CHEMISTRY (2021)

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Article Microbiology

Silver nanoparticles biosynthesized from secondary metabolite producing marine actinobacteria and evaluation of their biomedical potential

Ashia Alam et al.

Summary: The biosynthesis of silver nanoparticles from marine actinobacteria using extracellular extracts of Rhodococcus rhodochrous and Streptomyces sp. was studied for therapeutic applications. Characterization of the nanoparticles using various techniques revealed their potential for broad-spectrum antibacterial and anti-cancer activities, along with significant antioxidant properties and hemocompatibility. These findings suggest that biogenic AgNPs have diverse biological applications and marine actinobacteria are excellent resources for AgNPs fabrication.

ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY (2021)

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Review Microbiology

Targeting a highly conserved domain in bacterial histidine kinases to generate inhibitors with broad spectrum activity

Conrad A. Fihn et al.

Summary: Targeting bacterial signaling through two-component systems (TCSs) and developing inhibitors that target the HK ATP-binding domain may be effective strategies in combating antimicrobial resistance.

CURRENT OPINION IN MICROBIOLOGY (2021)

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Review Biochemistry & Molecular Biology

An Evolving Technology That Integrates Classical Methods with Continuous Technological Developments: Thin-Layer Chromatography Bioautography

Meng Wang et al.

Summary: Thin-layer chromatography (TLC) bioautography is an evolving technology that has gained popularity in recent decades. It is used for determining antibacterial, antifungal, antitumor, and antioxidant compounds, with potential for screening natural products with anti-COVID potential.

MOLECULES (2021)

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Article Biochemistry & Molecular Biology

Engineering of Streptoalloteichus tenebrarius 2444 for Sustainable Production of Tobramycin

Lena Mitousis et al.

Summary: The study successfully reduced the production of undesired product and increased the production of tobramycin by altering fermentation media and genetic engineering techniques. With cumulative improvements, this process enables more efficient and sustainable industrial-scale production of tobramycin.

MOLECULES (2021)

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Review Biochemistry & Molecular Biology

Membrane Sensor Histidine Kinases: Insights from Structural, Ligand and Inhibitor Studies of Full-Length Proteins and Signalling Domains for Antibiotic Discovery

Pikyee Ma et al.

Summary: There is an urgent need for new antibacterial agents to combat bacterial infections, with a focus on two-component signal transduction systems (TCSs). Despite technical challenges, recent advancements have been made in producing active SHKs, understanding signal sensing, and transduction mechanisms.

MOLECULES (2021)

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Article Microbiology

Beyond Self-Resistance: ABCF ATPase LmrC Is a Signal-Transducing Component of an Antibiotic-Driven Signaling Cascade Accelerating the Onset of Lincomycin Biosynthesis

Marketa Koberska et al.

Summary: This research demonstrates that antibiotic resistance proteins regulate lincomycin biosynthesis in response to subinhibitory concentrations of antibiotics. Specifically, the ABCF ATPase LmrC plays a dual role in providing antibiotic resistance while also transmitting a signal from ribosome-bound antibiotics to gene expression. This ABCF-mediated antibiotic signaling system may not only induce antibiotic biosynthesis but also selectively regulate gene expression in response to ribosome-targeting antibiotics.

MBIO (2021)

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Isolation, characterization, anti-MRSA evaluation, and in-silico multi-target anti-microbial validations of actinomycin X2 and actinomycin D produced by novel Streptomyces smyrnaeus UKAQ_23

Kamal A. Qureshi et al.

Summary: The new strain Streptomyces smyrnaeus UKAQ_23 isolated from mangrove sediment in Saudi Arabia showed substantial antimicrobial activity against MRSA and non-MRSA Gram-positive test bacteria, and produced a high yield of antimicrobial compounds, including Actinomycin X-2 and Actinomycin D. Actinomycin X-2 exhibited higher antimicrobial activity compared to Actinomycin D, making it a promising candidate for industrial production with potential benefits for the pharmaceutical industry.

SCIENTIFIC REPORTS (2021)

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Review Immunology

Bacterial Outer Membrane Vesicles as Antibiotic Delivery Vehicles

Shannon M. Collins et al.

Summary: Bacterial outer membrane vesicles (OMVs) play key roles in pathogenesis by delivering biomolecules to host cells, while also facilitating intra-bacterial communication processes, making them promising antibiotic delivery vehicles.

FRONTIERS IN IMMUNOLOGY (2021)

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Strategies of Detecting Bacteria Using Fluorescence-Based Dyes

Shin A. Yoon et al.

Summary: This review outlines recent advances in the development of fluorescence-based dyes for detecting bacteria, including strategies such as specific interactions, bacterial and intracellular enzyme reactions, and theranostic probes. Validation of these fluorescent probes using various biological models is also demonstrated, highlighting the importance of effective in vitro and in vivo detection of bacteria and development of antimicrobial agents for future research.

FRONTIERS IN CHEMISTRY (2021)

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Marcus Miethke et al.

Summary: There is a growing demand for novel antimicrobials to treat infections caused by multidrug-resistant bacterial pathogens, but there is currently a lack of investment in this field. New agents with innovative chemistry and modes of action are urgently needed to combat the public health threat posed by antimicrobial resistance. The consortium proposes short-term and long-term solutions to overcome urgent limitations in research and funding, aiming to bridge the gap between academic, industrial, and political stakeholders to improve the ability to discover and develop new antibiotics.

NATURE REVIEWS CHEMISTRY (2021)

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Minal M. Kshirsagar et al.

Summary: This study evaluated and compared the antibacterial efficacy of different commercially available dental gels, with Curenext gel showing the highest zone of inhibition against Streptococcus mutans and Lactobacillus acidophilus. The statistical analysis indicated a significant difference between the various dental gels.

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Coenzyme B12 controls transcription of the Streptomyces class Ia ribonucleotide reductase nrdABS operon via a riboswitch mechanism

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The bacterial ribosome as a target for antibiotics

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Panel of Bacillus subtilis reporter strains indicative of various modes of action

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Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species

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Amplified detection of transcriptional and translational inhibitors in bioluminescent Escherichia coli K-12

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Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics

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Structural and mutational analysis of the PhoQ histidine kinase catalytic domain. Insight into the reaction mechanism.

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