Bacterial genome sequencing and drug discovery

Allsop, Aileen

doi:10.1016/s0958-1669(98)80143-2

Cited by 26 publications

(12 citation statements)

References 47 publications

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“…Readers are advised to see the excellent articles published recently on genomics, functional genomics, and their application in novel drug target identification, validation and drug discovery [37,[44][45][46][47].…”

Section: Role Of Genomics In New Antibacterial Drug Discoverymentioning

confidence: 99%

Novel Approaches to Combat Drug‐Resistant Bacteria

Ahmad

Zahin

Aqil

et al. 2008

New Strategies Combating Bacterial Infection

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There is an increasing concern that the need for new antibacterial agents is greater than ever because of the emergence of multidrug resistance in common bacterial pathogens and the rapid emergence of new infections. Despite the critical need for new antibacterial agents, development is declining. Therefore, solutions for encouraging and facilitating the development of new agents are needed. It is believed that sustained success in the long-term battle against bacterial pathogens will require new strategies and new chemical scaffolds that target other cellular processes. In recent years, new antibacterial drug targets have been explored and validated. Some of the vulnerable targets are bacterial quorum sensing, interference with virulence and pathogenicity, drug-resistance mechanisms (efflux pump) and targets based on plasmid physiology. It is expected and believed by many workers that unexplored microbial diversity may provide novel and effective antibacterial drugs, if improved screening strategies are attempted and intelligent test systems are applied. This chapter will discuss recent strategies to obtain novel antibacterials from microbial products to combat drug-resistant bacteria. Further, roles of alternative therapy (phage therapy) and antibiotic use policy are discussed as possible ways to minimize the problem of drug resistant bacteria.

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Section: Role Of Genomics In New Antibacterial Drug Discoverymentioning

confidence: 99%

Novel Approaches to Combat Drug‐Resistant Bacteria

Ahmad

Zahin

Aqil

et al. 2008

New Strategies Combating Bacterial Infection

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“…1) should be different from existing targets, essential for microbial cell survival, highly conserved in a clinically‐relevant spectrum of species and absent or radically different in man. Inhibition of this activity could therefore cure the infection by killing the potential range of micro‐organisms involved without damaging the patient, and activity should not be restricted by existing resistance mechanisms (Allsop 1998). Furthermore, the ideal target should be easy to assay, ideally in high throughput mode, to identify inhibitors and to be suitable for rapid structural analysis.…”

Section: Genomics and Target Selectionmentioning

confidence: 99%

The impact of genomics and related technologies on the search for new antibiotics

Allsop

Illingworth

2002

J Appl Microbiol

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Over the past 20 years, the pharmaceutical industry has adopted a variety of strategies in the hunt for new antibiotics. Traditionally, the most successful approach has been random screening for new active molecules followed by chemical optimization, using simple antibiotic activity for primary selection. Until recently, more imaginative strategies were limited by knowledge and technology. The advent of microbial genomics has provided the information necessary to extend our knowledge into new areas of microbial physiology and to build the tools that will facilitate investigation. The aim of this paper is to demonstrate how microbial genomics is being used to discover and develop new antimicrobial agents, targeted at speci®c clinical needs. UNMET MEDICAL NEEDThe clinical need for new classes of antibiotic continues to grow, driven by drug resistance which erodes the ef®cacy of current therapies. Historically, most antibiotics were discovered by random screening campaigns but over the past 20 years, this strategy has largely failed to deliver a suf®cient range of chemical diversity to keep pace with changing clinical pro®les, particularly resistance. The urgency of this need is most critically experienced in the hospital environment (Struelens 1998;Kmietowicz 2000) although even in the community, choices are becoming limited for con®dent treatment

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“…A lot of novel scheme for the identification of bacterial drug targets has been pioneered by the available information of the bacterial genome sequences (Allsop 1998;Chan et al 2010). As many drawbacks like time-consuming, costly are found in traditional drug discovery methods, advanced genome-based technology has opened an attractive choice to identify drug targets to the researchers.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential drug targets and inhibitor of the pathogenic bacteria Shigella flexneri 2a through the subtractive genomic approach

Oany¹,

Mia²,

Pervin³

et al. 2018

In Silico Pharmacol.

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Shigella flexneri 2a is one of the most pathogenic bacteria among the Shigella spp., which is responsible for dysentery and causes masses of deaths throughout the world per year. A proper identification of the potential drug targets and inhibitors is crucial for the treatment of the shigellosis due to their emerging multidrug resistance (MDR) patterns. In this study, a systematic subtractive approach was implemented for the identification of novel therapeutic targets of S. flexneri 2a (301) through genome-wide metabolic pathway analysis of the essential genes and proteins. Ligand-based virtual screening and ADMET analyses were also made for the identification of potential inhibitors as well. Initially, we found 70 essential unique proteins as novel targets. After subsequent prioritization, finally we got six unique targets as the potential therapeutic targets and their three-dimensional models were built thereafter. Aspartate-β-semialdehyde dehydrogenase (ASD), was the most potent target among them and used for docking analysis through ligand-based virtual screening. The compound 3 (PubChem CID: 11319750) suited well as the best inhibitor of the ASD through ADMET and enzyme inhibition capacity analysis. To end, we hope that our proposed therapeutic targets and its inhibitors might give some breakthrough to treat shigellosis efficiently in in vitro.

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Bacterial genome sequencing and drug discovery

Cited by 26 publications

References 47 publications

Novel Approaches to Combat Drug‐Resistant Bacteria

Novel Approaches to Combat Drug‐Resistant Bacteria

The impact of genomics and related technologies on the search for new antibiotics

Identification of potential drug targets and inhibitor of the pathogenic bacteria Shigella flexneri 2a through the subtractive genomic approach

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