Properties and Identification of Antibiotic Drug Targets

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2010 Apr 22

PMID 20406434

Citations 11

Authors

Tala M Bakheet

Andrew J Doig

Affiliations

Soon will be listed here.

Abstract

Background: We analysed 48 non-redundant antibiotic target proteins from all bacteria, 22 antibiotic target proteins from E. coli only and 4243 non-drug targets from E. coli to identify differences in their properties and to predict new potential drug targets.

Results: When compared to non-targets, bacterial antibiotic targets tend to be long, have high beta-sheet and low alpha-helix contents, are polar, are found in the cytoplasm rather than in membranes, and are usually enzymes, with ligases particularly favoured. Sequence features were used to build a support vector machine model for E. coli proteins, allowing the assignment of any sequence to the drug target or non-target classes, with an accuracy in the training set of 94%. We identified 319 proteins (7%) in the non-target set that have target-like properties, many of which have unknown function. 63 of these proteins have significant and undesirable similarity to a human protein, leaving 256 target like proteins that are not present in humans.

Conclusions: We suggest that antibiotic discovery programs would be more likely to succeed if new targets are chosen from this set of target like proteins or their homologues. In particular, 64 are essential genes where the cell is not able to recover from a random insertion disruption.

Citing Articles

Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections.

Theuretzbacher U, Blasco B, Duffey M, Piddock L Nat Rev Drug Discov. 2023; 22(12):957-975.

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Covalent Proteomimetic Inhibitor of the Bacterial FtsQB Divisome Complex.

Paulussen F, Schouten G, Moertl C, Verheul J, Hoekstra I, Koningstein G J Am Chem Soc. 2022; 144(33):15303-15313.

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Core-Proteomics-Based Annotation of Antigenic Targets and Reverse-Vaccinology-Assisted Design of Ensemble Immunogen against the Emerging Nosocomial Infection-Causing Bacterium .

Idrees M, Noorani M, Altaf K, Alatawi E, Alkhayl F, Allemailem K Int J Environ Res Public Health. 2022; 19(1).

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In Silico Prediction and Prioritization of Novel Selective Antimicrobial Drug Targets in .

Frisinger F, Jana B, Donadio S, Guardabassi L Antibiotics (Basel). 2021; 10(6).

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Synergizing the potential of bacterial genomics and metabolomics to find novel antibiotics.

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PMID: 33995996 PMC: 8098685. DOI: 10.1039/d0sc06919a.

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