We explore other antibacterial strategies and continuously screen our collection of unique compounds for potential antibacterial agents. Through this work we have identified compounds potent against MRSA, anti-biofilm compounds, and compounds that induce plasmid elimination from bacterial cells.

As one example, the natural product deoxynybomycin (DMN) is extremely potent against Gram-positive bacteria that are resistant to fluoroquinolones (FQs). As ~100% of MRSA and VRE are FQ-resistant, there is medicinal promise for this compound class. In 2015 we reported the synthesis of DMN and multiple derivatives. One of these compounds, called DNM-2, has outstanding oral bioavailability and rescues mice infected with MRSA.

Related Publications:


Deoxynybomycins Inhibit Mutant DNA Gyrase and Rescue Mice Infected with Fluoroquinolone-Resistant Bacteria

Parkinson, E. I.; Bair, J. S.; Nakamura, B.; Lee, H. Y.; Kuttab, H. I.; Southgate, E. H.; Lezmi, S.; Lau, G. W.; Hergenrother, P. J.  

Nat. Commun. 20156, 6947.


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Identification of a Novel Protein Synthesis Inhibitor Active Against Gram-Positive Bacteria

Eibergen, N. R.; Im, I.; Patel, N. Y.; Hergenrother, P. J.

ChemBioChem 2012, 13, 574-583.


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Chelated Iron Sources are Inhibitors of Psudomonas aeruginosa Biofilms and Distribute Efficiently in an in vitro Model of Drug Delivery to the Human Lung

Musk, D. J.; Hergenrother, P. J.

J. Appl. Microbiol. 2008, 105, 380-388.


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Chemical Countermeasures for the Control of Bacterial Biofilms: Effective Compounds and Promising Targets

Musk, D. J.; Hergenrother, P. J.

Curr. Med. Chem. 2006, 13, 2163-2177 (review).


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Iron Salts Perturb Biofilm Formation and Disrupt Existing Biofilms of Pseudomonas aeruginosa

Musk, D. J.; Banko, D. A.; Hergenrother, P. J.

Chem. Biol. 2005, 12, 789-796.


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Chemistry & Biology Highlight


The Relationship Between Aminoglycosides' RNA Binding Proclivity and Their Antiplasmid Effect on an IncB Plasmid

Thomas, J. R.; DeNap, J. C. B.; Wong, M.; Hergenrother, P. J.

Biochemistry 2005, 44, 6800-6808.


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Bacterial Death comes Full Circle: Targeting Plasmid Replication in Drug-Resistant Bacteria

DeNap, J. C. B.; Hergenrother, P. J.

Org. Biomol. Chem. 2005, 3, 959-966.


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Combating Drug-Resistant Bacteria: Small Molecule Mimics of Plasmid Incompatibility as Antiplasmid Compounds

DeNap, J. B.; Thomas, J. R.; Musk, D. J.; Hergenrother, P. J.

J. Am. Chem. Soc. 2004, 126, 15402-15404.


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