A Bioengineered Three-Dimensional Cell Culture Platform Integrated with Microfluidics To Address Antimicrobial Resistance in Tuberculosis.
Magdalena K BieleckaLiku B TezeraRobert ZmijanFrancis DrobniewskiXunli ZhangSuwan JayasinghePaul T ElkingtonPublished in: mBio (2017)
Antimicrobial resistance is a major global threat, and an emerging concept is that infection should be studied in the context of host immune cells. Tuberculosis is a chronic infection that kills over a million people every year and is becoming progressively more resistant to antibiotics. Recent major studies of shorter treatment or new vaccination approaches have not been successful, demonstrating that transformative technologies are required to control tuberculosis. We have developed an entirely new system to study the infection of host cells in a three-dimensional matrix by using bioengineering. We showed that antibiotics that work in patients are effective in this microsphere system but not in standard infection systems. We then combined microspheres with microfluidics to model drug concentration changes in patients and demonstrate the effect of increasing antibiotic concentrations on bacterial survival. This system can be widely applied to address the threat of antimicrobial resistance and develop new treatments.
Keyphrases
- antimicrobial resistance
- end stage renal disease
- ejection fraction
- chronic kidney disease
- mycobacterium tuberculosis
- newly diagnosed
- peritoneal dialysis
- prognostic factors
- hiv aids
- induced apoptosis
- signaling pathway
- patient reported outcomes
- cell death
- oxidative stress
- mass spectrometry
- single cell
- drug induced
- combination therapy
- pi k akt