An epidemic of multidrug-resistant (MDR) bacterial infections continues to plague global and US health care, and with few new drugs making it to market from a diminished pipeline, there is an unmet medical need for new therapeutics to treat drug-resistant infections. Furthermore, effective therapies are urgently needed to address ongoing public health and biosecurity concerns that high-threat select agent bacteria can be engineered to become resistant to all currently available antibiotics. The central hypotheses of this Center application are that seeking novel compounds directly targeting MDR Gram-positive and Gram-negative pathogens has the greatest probability of finding new antibiotics, and that concerted collaboration among academic institutions and industry will accelerate the antibiotic drug discovery process. The mission of the Center is to support early drug discovery efforts, including target validation, chemical lead identification, structure-activity relationship analysis pharmacokinetics and in vivo therapeutic efficacy, and thereby develop optimized chemical Leads that are suitable candidates for preclinical evaluation. We propose in aims 1 and 2 to explore novel classes of compounds against proven targets with broad spectrum application, RNA polymerase and DNA gyrase;3) characterize novel compounds against mycolic acid biosynthesis in Mycobacterium tuberculosis;4) develop untapped environmentally-derived novel peptides, as a source for new antibiotics;and 5) use computational Bayesian modeling to accelerate antibacterial discovery. Critical success factors are the strength of Project Leaders with innovative drug discovery programs, and the inclusion of Trius Therapeutics, a biopharmaceutical company focused on antibiotic development. The Center is supported by an integrated infrastructure of support cores for compound optimization and access to the UMDNJ Regional Biocontainment Lab for pathogen studies. The overall program will be guided by David Perlin, an accomplished translational researcher and administrator, a Scientific Advisory Committee including members of Pharma, and a solid operations and management team that can effectively manage large translational research programs and promote licensing opportunities.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Parker, Tina M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Rutgers University
Public Health & Prev Medicine
Schools of Medicine
United States
Zip Code
Kumar, Pradeep; Capodagli, Glenn C; Awasthi, Divya et al. (2018) Synergistic Lethality of a Binary Inhibitor of Mycobacterium tuberculosis KasA. MBio 9:
Nukaga, Michiyoshi; Papp-Wallace, Krisztina M; Hoshino, Tyuji et al. (2018) Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam. Antimicrob Agents Chemother 62:
Becka, Scott A; Zeiser, Elise T; Marshall, Steven H et al. (2018) Sequence heterogeneity of the PenA carbapenemase in clinical isolates of Burkholderia multivorans. Diagn Microbiol Infect Dis 92:253-258
Vila-Farres, Xavier; Chu, John; Ternei, Melinda A et al. (2018) An Optimized Synthetic-Bioinformatic Natural Product Antibiotic Sterilizes Multidrug-Resistant Acinetobacter baumannii-Infected Wounds. mSphere 3:
Papp-Wallace, Krisztina M; Barnes, Melissa D; Alsop, Jim et al. (2018) Relebactam Is a Potent Inhibitor of the KPC-2 ?-Lactamase and Restores Imipenem Susceptibility in KPC-Producing Enterobacteriaceae. Antimicrob Agents Chemother 62:
Lane, Thomas; Russo, Daniel P; Zorn, Kimberley M et al. (2018) Comparing and Validating Machine Learning Models for Mycobacterium tuberculosis Drug Discovery. Mol Pharm 15:4346-4360
Papp-Wallace, Krisztina M; Nguyen, Nhu Q; Jacobs, Michael R et al. (2018) Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using ?-Lactamase Inhibitors and ?-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234. J Med Chem 61:4067-4086
Lin, Wei; Das, Kalyan; Degen, David et al. (2018) Structural Basis of Transcription Inhibition by Fidaxomicin (Lipiarmycin A3). Mol Cell 70:60-71.e15
Inoyama, Daigo; Paget, Steven D; Russo, Riccardo et al. (2018) Novel Pyrimidines as Antitubercular Agents. Antimicrob Agents Chemother 62:
Becka, Scott A; Zeiser, Elise T; Barnes, Melissa D et al. (2018) Characterization of the AmpC ?-Lactamase from Burkholderia multivorans. Antimicrob Agents Chemother 62:

Showing the most recent 10 out of 23 publications