Point of care detection of fluroquinolone, bedaquiline and linezolid resistant mycobacterium tuberculosis for rapid treatment decisions
Active Project Grant Awarded Last action
- Award ID
- R01AI182257
- Recipient
-
Rutgers The State University Of New Jersey UEI YVVTQD8CJC79
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,853,282
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 55% complete
- Place of performance
- Newark, NJ 07107, USA
Award details come from USAspending.gov.
Description
- Abstract
- Rapid and sensitive point of care tests that can detect all forms of drug resistance are urgently needed to enable appropriate treatment for TB. Molecular drug susceptibility tests (mdsts) which use nucleic acid amplification techniques to detect mutations associated with resistance to the primary tuberculosis (TB) drugs isoniazid (INH), and rifampin (RIF), and in a few rare cases fluoroquinolones (FQS) have demonstrated the potential of this susceptibility testing approach. However, current mdsts are unable to detect the large numbers of mutations which encode for resistance to the critical new anti-tubercular drug, bedaquiline (BDQ), and linezolid (LZD). These new drugs along with FQS and another new drug pretominid (PA) comprise the backbone of the most promising TB treatments of the future. Yet, without the availability of companion mdsts, the world risks losing these new drugs to drug resistance within a few years of deployment. We propose to use innovative new fluidic and assay designs to enable detection of hundreds of different mutations encoding FQ, LZD, and BDQ resistance using the standard cepheid assay cartridge. This new test would retain all the advantages of current cepheid TB assays, a robust manufacturing and instrument placement base enabled by the high volume of assays currently produced. This research program will include 4 aims. Aim 1. Develop MIS-match tolerant or "sloppy" molecular beacons (smbs) that identify mutations associated with FQ and LZD resistance that are optimized for ultimate use in the new three-phase highly multiplex system to be developed in this grant. Aim 2. BDQ assay development detecting mutations in atpe and a new SMB tiling approach that queries the entire MTB RV0678 gene to identify mutations causal of BDQ resistance. Aim 3 optimize three-phase cartridge fluidics for highly multiplex mutation detection. Aim 4. Perform an initial laboratory and clinical validation study of the final aim 1-3 assays using stored clinical samples.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $782,450 | |
| Amendment | $758,976 | |
| Amendment | $78,244 | |
| Amendment | $78,244 | |
| Amendment | $718,456 | |
| Amendment | $718,456 | |
| Original award | $718,456 |
Subawards
Quick answers
Who received award R01AI182257?
R01AI182257 was awarded to Rutgers The State University Of New Jersey by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on February 26, 2024.
How much is award R01AI182257 worth?
$3,853,282 has been obligated on R01AI182257.
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