Imperial College London
Alternate

Professor Angelika Gründling

Faculty of Medicine, Department of Infectious Disease

Professor of Molecular Microbiology
 
 
 
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Contact

 

+44 (0)20 7594 5256a.grundling Website

 
 
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Location

 

6.22Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Meredith:2012:10.4161/mge.21647,
author = {Meredith, TC and Wang, H and Beaulieu, P and Gründling, A and Roemer, T},
doi = {10.4161/mge.21647},
journal = {Mob Genet Elements},
pages = {171--178},
title = {Harnessing the power of transposon mutagenesis for antibacterial target identification and evaluation.},
url = {http://dx.doi.org/10.4161/mge.21647},
volume = {2},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Determining the mechanism of action of bacterial growth inhibitors can be a formidable challenge in the progression of small molecules into antibacterial therapies. To help address this bottleneck, we have developed a robust transposon mutagenesis system using a suite of outward facing promoters in order to generate a comprehensive range of expression genotypes in Staphylococcus aureus from which to select defined compound-resistant transposon insertion mutants. Resistance stemming from either gene or operon over/under-expression, in addition to deletion, provides insight into multiple factors that contribute to a compound's observed activity, including means of cell envelope penetration and susceptibility to efflux. By profiling the entire resistome, the suitability of an antibacterial target itself is also evaluated, sometimes with unanticipated results. We herein show that for the staphylococcal signal peptidase (SpsB) inhibitors, modulating expression of lipoteichoic acid synthase (LtaS) confers up to a 100-fold increase in the minimal inhibitory concentration. As similarly efficient transposition systems are or will become established in other bacteria and cell types, we discuss the utility, limitations and future promise of Tnp mutagenesis for determining both a compound's mechanism of action and in the evaluation of novel targets.
AU  - Meredith,TC
AU  - Wang,H
AU  - Beaulieu,P
AU  - Gründling,A
AU  - Roemer,T
DO  - 10.4161/mge.21647
EP  - 178
PY  - 2012///
SN  - 2159-2543
SP  - 171
TI  - Harnessing the power of transposon mutagenesis for antibacterial target identification and evaluation.
T2  - Mob Genet Elements
UR  - http://dx.doi.org/10.4161/mge.21647
UR  - https://www.ncbi.nlm.nih.gov/pubmed/23094235
VL  - 2
ER  -
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