Imperial College London
Alternate

Professor Francis Drobniewski

Faculty of Medicine, Department of Infectious Disease

Chair in Global Health and Tuberculosis
 
 
 
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Contact

 

f.drobniewski

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bielecka:2017:10.1128/mBio.02073-16,
author = {Bielecka, MK and Tezera, LB and Zmijan, R and Drobniewski, F and Zhang, X and Jayasinghe, S and Elkington, P},
doi = {10.1128/mBio.02073-16},
journal = {MBIO},
title = {A bioengineered three-dimensional cell culture platform integrated with microfluidics to address antimicrobial resistance in tuberculosis},
url = {http://dx.doi.org/10.1128/mBio.02073-16},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Antimicrobial resistance presents one of the most significant threats to human health, with the emergence of totally drug-resistant organisms. We have combined bioengineering, genetically modified bacteria, longitudinal readouts, and fluidics to develop a transformative platform to address the drug development bottleneck, utilizing Mycobacterium tuberculosis as the model organism. We generated microspheres incorporating virulent reporter bacilli, primary human cells, and an extracellular matrix by using bioelectrospray methodology. Granulomas form within the three-dimensional matrix, and mycobacterial stress genes are upregulated. Pyrazinamide, a vital first-line antibiotic for treating human tuberculosis, kills M. tuberculosis in a three-dimensional culture but not in a standard two-dimensional culture or Middlebrook 7H9 broth, demonstrating that antibiotic sensitivity within microspheres reflects conditions in patients. We then performed pharmacokinetic modeling by combining the microsphere system with a microfluidic plate and demonstrated that we can model the effect of dynamic antibiotic concentrations on mycobacterial killing. The microsphere system is highly tractable, permitting variation of cell content, the extracellular matrix, sphere size, the infectious dose, and the surrounding medium with the potential to address a wide array of human infections and the threat of antimicrobial resistance.
AU  - Bielecka,MK
AU  - Tezera,LB
AU  - Zmijan,R
AU  - Drobniewski,F
AU  - Zhang,X
AU  - Jayasinghe,S
AU  - Elkington,P
DO  - 10.1128/mBio.02073-16
PY  - 2017///
SN  - 2150-7511
TI  - A bioengineered three-dimensional cell culture platform integrated with microfluidics to address antimicrobial resistance in tuberculosis
T2  - MBIO
UR  - http://dx.doi.org/10.1128/mBio.02073-16
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000395835000004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/45024
VL  - 8
ER  -
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