Iron Acquisition and Metabolism as a Promising Target for Antimicrobials (Bottlenecks and Opportunities): Where Do We Stand?

In vitro activity of newer β-lactam/β-lactamase inhibitor combinations, cefiderocol, plazomicin and comparators against carbapenemase-producing Klebsiella pneumoniae isolates

(2023) Sofia Maraki et al.   JOURNAL OF CHEMOTHERAPY

Targeting Siderophore-Mediated Iron Uptake in M. abscessus: A New Strategy to Limit the Virulence of Non-Tuberculous Mycobacteria

(2023) Matteo Mori et al.   Pharmaceutics

Antimicrobial Activity of Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Cefiderocol, and Novel Darobactin Analogs against Multidrug-Resistant Pseudomonas aeruginosa Isolates from Pediatric and Adolescent Cystic Fibrosis Patients

(2023) Michael Marner et al.   Microbiology Spectrum

Cefiderocol, a Siderophore Cephalosporin, as a Treatment Option for Infections Caused by Carbapenem-Resistant Enterobacterales

(2023) Keith S. Kaye et al.   Infectious Diseases and Therapy

Gallium(III)-Mediated Dual-Cross-Linked Alginate Hydrogels with Antibacterial Properties for Promoting Infected Wound Healing

(2022) Jiajun Qin et al.   ACS Applied Materials & Interfaces

Synthesis and in vitro analysis of novel gallium tetrakis(4-methoxyphenyl)porphyrin and its long-acting nanoparticle as a potent antimycobacterial agent

(2022) Seoung-ryoung Choi et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Antimicrobial Activity of the Iron-Chelator, DIBI, against Multidrug-Resistant Canine Methicillin-Susceptible Staphylococcus pseudintermedius: A Preliminary Study of Four Clinical Strains

(2022) Francesca Paola Nocera et al.   Pathogens

Synthesis and Assessment of the In Vitro and Ex Vivo Activity of Salicylate Synthase (Mbti) Inhibitors as New Candidates for the Treatment of Mycobacterial Infections

(2022) Matteo Mori et al.   Pharmaceuticals

Gallium protoporphyrin as an antimicrobial for non-typeable Haemophilus influenzae in COPD patients

(2022) James M. Baker et al.   LIFE SCIENCES

Gallium ions incorporated silk fibroin hydrogel with antibacterial efficacy for promoting healing of Pseudomonas aeruginosa-infected wound

(2022) Hui Zheng et al.   Frontiers in Chemistry

Synthesis and study of new siderophore analog-ciprofloxacin conjugates with antibiotic activities against Pseudomonas aeruginosa and Burkholderia spp.

(2022) P. Loupias et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Boosting lung accumulation of gallium with inhalable nano-embedded microparticles for the treatment of bacterial pneumonia

(2022) Gabriella Costabile et al.   INTERNATIONAL JOURNAL OF PHARMACEUTICS

Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance

(2022) Patrick Munk et al.   Nature Communications

Cefiderocol against Multi-Drug and Extensively Drug-Resistant Escherichia coli: An In Vitro Study in Poland

(2022) Patrycja Zalas-Więcek et al.   Pathogens

Design and Syntheses of New Antibiotics Inspired by Nature’s Quest for Iron in an Oxidative Climate

(2021) Marvin J. Miller et al.   ACCOUNTS OF CHEMICAL RESEARCH

Synthesis, Characterization, and Biological Evaluation of New Derivatives Targeting MbtI as Antitubercular Agents

(2021) Matteo Mori et al.   Pharmaceuticals

Iron Acquisition Systems of Gram-negative Bacterial Pathogens Define TonB-Dependent Pathways to Novel Antibiotics

(2021) Phillip E. Klebba et al.   CHEMICAL REVIEWS

Iron-withdrawing anti-infectives for new host-directed therapies based on iron dependence, the Achilles’ heel of antibiotic-resistant microbes

(2021) Bruce E. Holbein et al.   Environmental Chemistry Letters

Environmental hotspots for antibiotic resistance genes

(2021) Shalini Kunhikannan et al.   MicrobiologyOpen

Intra-tracheal administration increases gallium availability in lung: implications for antibacterial chemotherapy

(2021) Emma Mitidieri et al.   PHARMACOLOGICAL RESEARCH

Nanoparticulate β-Cyclodextrin with Gallium Tetraphenylporphyrin Demonstrates in Vitro and in Vivo Antimicrobial Efficacy against Mycobacteroides abscessus and Mycobacterium avium

(2021) Seoung-Ryoung Choi et al.   ACS Infectious Diseases

Pyoverdine Inhibitors and Gallium Nitrate Synergistically Affect Pseudomonas aeruginosa

(2021) Donghoon Kang et al.   mSphere

Natural products against key Mycobacterium tuberculosis enzymatic targets: Emerging opportunities for drug discovery

(2021) Giulia Cazzaniga et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Monitoring antibiotic resistance genes in wastewater environments: The challenges of filling a gap in the One-Health cycle

(2021) Aleksandra Miłobedzka et al.   JOURNAL OF HAZARDOUS MATERIALS

Antibiotic Conjugates with an Artificial MECAM-Based Siderophore Are Potent Agents against Gram-Positive and Gram-Negative Bacterial Pathogens

(2021) Lukas Pinkert et al.   JOURNAL OF MEDICINAL CHEMISTRY

Variable Susceptibility to Gallium Compounds of Major Cystic Fibrosis Pathogens

(2021) Daniela Visaggio et al.   ACS Infectious Diseases

Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects

(2021) Tanvir Mahtab Uddin et al.   Journal of Infection and Public Health

Iron Sequestrant DIBI, a Potential Alternative for Nares Decolonization of Methicillin-Resistant Staphylococcus aureus, Is Anti-infective and Inhibitory for Mupirocin-Resistant Isolates

(2020) David S. Allan et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Antivirulence compounds: a future direction to overcome antibiotic resistance?

(2020) Silvia Buroni et al.   Future Microbiology

Polyglycerol-Based Macromolecular Iron Chelator Adjuvants for Antibiotics To Treat Drug-Resistant Bacteria

(2020) Srinivas Abbina et al.   ACS Applied Materials & Interfaces

Shedding X-ray Light on the Role of Magnesium in the Activity of Mycobacterium tuberculosis Salicylate Synthase (MbtI) for Drug Design

(2020) Matteo Mori et al.   JOURNAL OF MEDICINAL CHEMISTRY

Gallium(III)–Salophen as a Dual Inhibitor of Pseudomonas aeruginosa Heme Sensing and Iron Acquisition

(2020) Garrick Centola et al.   ACS Infectious Diseases

In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains

(2020) Le Phuong Nguyen et al.   Antibiotics-Basel

Role of post‐translational modifications in the acquisition of drug resistance in Mycobacterium tuberculosis

(2020) Gunjan Arora et al.   FEBS Journal

Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial

(2020) Matteo Bassetti et al.   LANCET INFECTIOUS DISEASES

Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial

(2020) Richard G Wunderink et al.   LANCET INFECTIOUS DISEASES

Gallium Porphyrin and Gallium Nitrate Synergistically Inhibit Mycobacterial Species by Targeting Different Aspects of Iron/Heme Metabolism

(2020) Seoung-ryoung Choi et al.   ACS Infectious Diseases

Harnessing Iron Acquisition Machinery to Target Enterobacteriaceae

(2020) Artur Sargun et al.   JOURNAL OF INFECTIOUS DISEASES

The Mycobactin Biosynthesis Pathway: A Prospective Therapeutic Target in the Battle against Tuberculosis

(2020) Mousumi Shyam et al.   JOURNAL OF MEDICINAL CHEMISTRY

Platform to Discover Protease-Activated Antibiotics and Application to Siderophore–Antibiotic Conjugates

(2020) Jonathan H. Boyce et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Novel Pyoverdine Inhibitors Mitigate Pseudomonas aeruginosa Pathogenesis

(2019) Daniel R. Kirienko et al.   Frontiers in Microbiology

New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents

(2019) Laurent R. Chiarelli et al.   JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Iron/Heme Metabolism-Targeted Gallium(III) Nanoparticles Are Active against Extracellular and Intracellular Pseudomonas aeruginosa and Acinetobacter baumannii

(2019) Seoung-ryoung Choi et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Drug delivery systems designed to overcome antimicrobial resistance

(2019) Thanh‐Nhat Pham et al.   MEDICINAL RESEARCH REVIEWS

Recent Advances in Anti-virulence Therapeutic Strategies With a Focus on Dismantling Bacterial Membrane Microdomains, Toxin Neutralization, Quorum-Sensing Interference and Biofilm Inhibition

(2019) Osmel Fleitas Martínez et al.   Frontiers in Cellular and Infection Microbiology

Antibiotic resistant Acinetobacter baumannii is susceptible to the novel iron-sequestering anti-infective DIBI in vitro and in experimental pneumonia in mice

(2019) Maria del Carmen Parquet et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Dual Inhibition of Klebsiella pneumoniae and Pseudomonas aeruginosa Iron Metabolism Using Gallium Porphyrin and Gallium Nitrate

(2019) Seoung-ryoung Choi et al.   ACS Infectious Diseases

Integrated Target‐Based and Phenotypic Screening Approaches for the Identification of Anti‐Tubercular Agents That Bind to the Mycobacterial Adenylating Enzyme MbtA

(2019) Lindsay Ferguson et al.   ChemMedChem

The Role of Iron and Siderophores in Infection, and the Development of Siderophore Antibiotics

(2019) Malcom G P Page   CLINICAL INFECTIOUS DISEASES

Bacterial siderophores in community and host interactions

(2019) Jos Kramer et al.   NATURE REVIEWS MICROBIOLOGY

A novel mechanism of inhibition by phenylthiourea on PvdP, a tyrosinase synthesizing pyoverdine of Pseudomonas aeruginosa

(2019) Joko P. Wibowo et al.   INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Pharmacokinetics, Safety, and Tolerability of Cefiderocol, a Novel Siderophore Cephalosporin for Gram-Negative Bacteria, in Healthy Subjects

(2018) Yutaka Saisho et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

New fluorescent rosamine chelator showing promising antibacterial activity against Gram-positive bacteria

(2018) Ângela Novais et al.   BIOORGANIC CHEMISTRY

Nonribosomal peptides for iron acquisition: pyochelin biosynthesis as a case study

(2018) Trey A Ronnebaum et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Cefiderocol (S-649266), A new siderophore cephalosporin exhibiting potent activities against Pseudomonas aeruginosa and other gram-negative pathogens including multi-drug resistant bacteria: Structure activity relationship

(2018) Toshiaki Aoki et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery and development of novel salicylate synthase (MbtI) furanic inhibitors as antitubercular agents

(2018) Laurent R. Chiarelli et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A Synthetic Dual Drug Sideromycin Induces Gram-Negative Bacteria To Commit Suicide with a Gram-Positive Antibiotic

(2018) Rui Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

New Chromane-Based Derivatives as Inhibitors of Mycobacterium tuberculosis Salicylate Synthase (MbtI): Preliminary Biological Evaluation and Molecular Modeling Studies

(2018) Elena Pini et al.   MOLECULES

DIBI, a 3-hydroxypyridin-4-one chelator iron-binding polymer with enhanced antimicrobial activity

(2018) M. Trisha C. Ang et al.   MedChemComm

Conformationally Constrained Cinnolinone Nucleoside Analogues as Siderophore Biosynthesis Inhibitors for Tuberculosis

(2018) Surendra Dawadi et al.   ACS Medicinal Chemistry Letters

Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function

(2018) Ankur Bothra et al.   Scientific Reports

The MmpS6-MmpL6 operon is an oxidative stress response system providing selective advantage to Mycobacterium tuberculosis in stress

(2018) Prabhakar Arumugam et al.   JOURNAL OF INFECTIOUS DISEASES

Gallium disrupts bacterial iron metabolism and has therapeutic effects in mice and humans with lung infections

(2018) Christopher H. Goss et al.   Science Translational Medicine

Antimicrobial Activity of Gallium Compounds on ESKAPE Pathogens

(2018) Sarah Hijazi et al.   Frontiers in Cellular and Infection Microbiology

Novel Iron-Chelator DIBI Inhibits Staphylococcus aureus Growth, Suppresses Experimental MRSA Infection in Mice and Enhances the Activities of Diverse Antibiotics in vitro

(2018) Maria del Carmen Parquet et al.   Frontiers in Microbiology

Siderophore Conjugates of Daptomycin are Potent Inhibitors of Carbapenem Resistant Strains of Acinetobacter baumannii

(2018) Manuka Ghosh et al.   ACS Infectious Diseases

Iron Acquisition in Mycobacterium tuberculosis

(2018) Alex Chao et al.   CHEMICAL REVIEWS

Drug repurposing: progress, challenges and recommendations

(2018) Sudeep Pushpakom et al.   NATURE REVIEWS DRUG DISCOVERY

Targeted Antibiotic Delivery: Selective Siderophore Conjugation with Daptomycin Confers Potent Activity against Multidrug Resistant Acinetobacter baumannii Both in Vitro and in Vivo

(2017) Manuka Ghosh et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis of Transition-State Inhibitors of Chorismate Utilizing Enzymes from Bromobenzene cis-1,2-Dihydrodiol

(2017) Xiao-Kang Zhang et al.   JOURNAL OF ORGANIC CHEMISTRY

Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance

(2017) Seth W. Dickey et al.   NATURE REVIEWS DRUG DISCOVERY

The therapeutic potential of iron-targeting gallium compounds in human disease: From basic research to clinical application

(2017) Christopher R. Chitambar   PHARMACOLOGICAL RESEARCH

Gallium-Protoporphyrin IX Inhibits Pseudomonas aeruginosa Growth by Targeting Cytochromes

(2017) Sarah Hijazi et al.   Frontiers in Cellular and Infection Microbiology

High-Throughput Genetic Screen Reveals that Early Attachment and Biofilm Formation Are Necessary for Full Pyoverdine Production by Pseudomonas aeruginosa

(2017) Donghoon Kang et al.   Frontiers in Microbiology

Gallium and its competing roles with iron in biological systems

(2016) Christopher R. Chitambar   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Synthesis of novel Iron(III) chelators based on triaza macrocycle backbone and 1-hydroxy-2(H)-pyridin-2-one coordinating groups and their evaluation as antimicrobial agents

(2016) David G. Workman et al.   JOURNAL OF INORGANIC BIOCHEMISTRY

Alternatives to antibiotics—a pipeline portfolio review

(2016) Lloyd Czaplewski et al.   LANCET INFECTIOUS DISEASES

A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence

(2016) Daniel R. Kirienko et al.   mSphere

Investigation of the multifaceted iron acquisition strategies of Burkholderia cenocepacia

(2015) J. Tyrrell et al.   BIOMETALS

Hexadentate 3-hydroxypyridin-4-ones with high iron(III) affinity: Design, synthesis and inhibition on methicillin resistant Staphylococcus aureus and Pseudomonas strains

(2015) Ying-Jun Zhou et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Synthesis and Pharmacokinetic Evaluation of Siderophore Biosynthesis Inhibitors for Mycobacterium tuberculosis

(2015) Kathryn M. Nelson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Investigation and Conformational Analysis of Fluorinated Nucleoside Antibiotics Targeting Siderophore Biosynthesis

(2015) Surendra Dawadi et al.   JOURNAL OF ORGANIC CHEMISTRY

Stereocontrolled Synthesis of a Potential Transition-State Inhibitor of the Salicylate Synthase MbtI from Mycobacterium tuberculosis

(2015) Zheng Liu et al.   JOURNAL OF ORGANIC CHEMISTRY

Tackling antibiotic resistance: the environmental framework

(2015) Thomas U. Berendonk et al.   NATURE REVIEWS MICROBIOLOGY

Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy

(2015) Matthew F. Barber et al.   TRENDS IN GENETICS

Identification of Inhibitors of PvdQ, an Enzyme Involved in the Synthesis of the Siderophore Pyoverdine

(2014) Jacqueline M. Wurst et al.   ACS Chemical Biology

Pyochelin Potentiates the Inhibitory Activity of Gallium on Pseudomonas aeruginosa

(2014) Emanuela Frangipani et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

n-Alkylboronic Acid Inhibitors Reveal Determinants of Ligand Specificity in the Quorum-Quenching and Siderophore Biosynthetic Enzyme PvdQ

(2014) Kenneth D. Clevenger et al.   BIOCHEMISTRY

Expanding the results of a high throughput screen against an isochorismate-pyruvate lyase to enzymes of a similar scaffold or mechanism

(2014) Kathleen M. Meneely et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Synthesis and antibacterial activity of catecholate–ciprofloxacin conjugates

(2014) Sylvain Fardeau et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Pharmacokinetic andIn VivoEfficacy Studies of the Mycobactin Biosynthesis Inhibitor Salicyl-AMS in Mice

(2013) Shichun Lun et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Pseudomonas aeruginosa Disrupts Caenorhabditis elegans Iron Homeostasis, Causing a Hypoxic Response and Death

(2013) Natalia V. Kirienko et al.   Cell Host & Microbe

Synthesis of Chromone, Quinolone, and Benzoxazinone Sulfonamide Nucleosides as Conformationally Constrained Inhibitors of Adenylating Enzymes Required for Siderophore Biosynthesis

(2013) Curtis A. Engelhart et al.   JOURNAL OF ORGANIC CHEMISTRY

Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity

(2013) F. Imperi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Transcriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic bacteria

(2013) Bryan Troxell et al.   Frontiers in Cellular and Infection Microbiology

Chemical syntheses and in vitro antibacterial activity of two desferrioxamine B-ciprofloxacin conjugates with potential esterase and phosphatase triggered drug release linkers

(2012) Cheng Ji et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Synthesis and antibacterial activity of conjugates between norfloxacin and analogues of the siderophore vanchrobactin

(2012) Alba Souto et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Synthesis and evaluation of M. tuberculosis salicylate synthase (MbtI) inhibitors designed to probe plasticity in the active site

(2012) Alexandra Manos-Turvey et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Antibiotic resistance is ancient

(2011) Vanessa M. D’Costa et al.   NATURE

Inhibition Studies of Mycobacterium tuberculosis Salicylate Synthase (MbtI)

(2010) Alexandra Manos-Turvey et al.   ChemMedChem

Inhibitors of the Salicylate Synthase (MbtI) from Mycobacterium tuberculosis Discovered by High-Throughput Screening

(2010) Mahalakshmi Vasan et al.   ChemMedChem

Recent advances in siderophore biosynthesis

(2009) Sarah M Barry et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Inhibition of Siderophore Biosynthesis inMycobacterium tuberculosiswith Nucleoside Bisubstrate Analogues: Structure−Activity Relationships of the Nucleobase Domain of 5′-O-[N-(Salicyl)sulfamoyl]adenosine

(2008) João Neres et al.   JOURNAL OF MEDICINAL CHEMISTRY