Abstract
New antibiotics with novel modes of action are required to combat the growing threat posed by multi-drug resistant bacteria. Over the last decade, genome sequencing and other high-throughput techniques have provided tremendous insight into the molecular processes underlying cellular functions in a wide range of bacterial species. We can now use these data to assess the degree of conservation of certain aspects of bacterial physiology, to help choose the best cellular targets for development of new broad-spectrum antibacterials.
DNA replication is a conserved and essential process, and the large number of proteins that interact to replicate DNA in bacteria are distinct from those in eukaryotes and archaea; yet none of the antibiotics in current clinical use acts directly on the replication machinery. Bacterial DNA synthesis thus appears to be an underexploited drug target. However, before this system can be targeted for drug design, it is important to understand which parts are conserved and which are not, as this will have implications for the spectrum of activity of any new inhibitors against bacterial species, as well as the potential for development of drug resistance. In this review we assess similarities and differences in replication components and mechanisms across the bacteria, highlight current progress towards the discovery of novel replication inhibitors, and suggest those aspects of the replication machinery that have the greatest potential as drug targets.
Keywords: DnaB, DnaC, DnaE, DNA polymerase IIIC, DnaG primase, helicase, Staphylococcus aureus, pthogens, genome sequencing, DNA replication
Current Drug Targets
Title: Architecture and Conservation of the Bacterial DNA Replication Machinery, an Underexploited Drug Target
Volume: 13 Issue: 3
Author(s): Andrew Robinson, Rebecca J. Causer and Nicholas E. Dixon
Affiliation:
Keywords: DnaB, DnaC, DnaE, DNA polymerase IIIC, DnaG primase, helicase, Staphylococcus aureus, pthogens, genome sequencing, DNA replication
Abstract: New antibiotics with novel modes of action are required to combat the growing threat posed by multi-drug resistant bacteria. Over the last decade, genome sequencing and other high-throughput techniques have provided tremendous insight into the molecular processes underlying cellular functions in a wide range of bacterial species. We can now use these data to assess the degree of conservation of certain aspects of bacterial physiology, to help choose the best cellular targets for development of new broad-spectrum antibacterials.
DNA replication is a conserved and essential process, and the large number of proteins that interact to replicate DNA in bacteria are distinct from those in eukaryotes and archaea; yet none of the antibiotics in current clinical use acts directly on the replication machinery. Bacterial DNA synthesis thus appears to be an underexploited drug target. However, before this system can be targeted for drug design, it is important to understand which parts are conserved and which are not, as this will have implications for the spectrum of activity of any new inhibitors against bacterial species, as well as the potential for development of drug resistance. In this review we assess similarities and differences in replication components and mechanisms across the bacteria, highlight current progress towards the discovery of novel replication inhibitors, and suggest those aspects of the replication machinery that have the greatest potential as drug targets.
Export Options
About this article
Cite this article as:
Robinson Andrew, J. Causer Rebecca and E. Dixon Nicholas, Architecture and Conservation of the Bacterial DNA Replication Machinery, an Underexploited Drug Target, Current Drug Targets 2012; 13 (3) . https://dx.doi.org/10.2174/138945012799424598
DOI https://dx.doi.org/10.2174/138945012799424598 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Diethyldithiocarbamate complex with copper: the mechanism of action in cancer cells
Mini-Reviews in Medicinal Chemistry Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy
Recent Patents on Anti-Cancer Drug Discovery Recent Progress in Molecular Mechanisms of Angiotensin II Type 1 and 2 Receptors
Current Pharmaceutical Design A Pathogenetic Approach to Autoimmune Skin Disease Therapy: Psoriasis and Biological Drugs, Unresolved Issues, and Future Directions
Current Pharmaceutical Design Molecular Mechanisms Regulating Matrix Metalloproteinases
Current Topics in Medicinal Chemistry Beneficial Action of Citrus Flavonoids on Multiple Cancer-Related Biological Pathways
Current Cancer Drug Targets Inflammatory Responses in Brain Ischemia
Current Medicinal Chemistry Commentary: Participation of Sox-1 Expression and Signaling of β-Catenin in the Pathophysiology of Generalized Seizures in Cerebellum of Rat
CNS & Neurological Disorders - Drug Targets Living Life to the Fullest: Early Integration of Palliative Care into the Lives of Children with Chronic Complex Conditions
Current Pediatric Reviews The Complex Biology of FOXO
Current Drug Targets Adenosine and Stroke: Maximizing the Therapeutic Potential of Adenosine as a Prophylactic and Acute Neuroprotectant
Current Neuropharmacology SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives
Current Medicinal Chemistry Erlotinib: A Targeted Anticancer Drug
Current Cancer Therapy Reviews Synergistic Effect of the Combination of Novel Suberoylanilide Hydroxamic Acid Derivatives with Cisplatin on Anti-proliferation of Human Cancer Cells
Medicinal Chemistry The Muscular Dystrophies Associated with Central Nervous System Lesions: A Brief Review from a Standpoint of the Localization and Function of Causative Genes
Current Pediatric Reviews Calcium Sensitizers in Cardiac Surgery: Who, When, How and Why?
Current Vascular Pharmacology Polyunsaturated Fatty Acids in Pregnancy and Metabolic Syndrome: A Review
Current Pharmaceutical Biotechnology The Development of Preventives and Therapeutics for Alzheimers Disease that Inhibit the Formation of β-Amyloid Fibrils (fAβ), as Well as Destabilize Preformed fAβ
Current Pharmaceutical Design WITHDRAWN: ESBLA: An Edge-Significance Based Modified Louvain Algorithm for Event Detection from Tweets
Recent Advances in Computer Science and Communications PiWi RNA in Neurodevelopment and Neurodegenerative Disorders
Current Molecular Pharmacology