Other Antibacterial Compounds

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.

Ying-Yang style diagram showing a compound called DNM-2, and another CIP.

Related Publications:

  1. Structures of the Staphylococcus aureus ribosome inhibited by fusidic acid and fusidic acid cyclopentane
    Gonzalez-Lopez A, Larsson DSD, Koripella RK, Cain BN, Sanyal S, Chavez MG, Hergenrother PJ, Sanyal S, Selmer M  
    Sci. Rep. 2024, 14, 14253
  1. Synthesis of fusidic acid derivatives yields a potent antibiotic with an improved resistance profile
    Garcia Chavez, M.; Garcia, A.; Lee, H.Y.; Lau, G.W.; Parker, E.N.; Komnick, K.E.; Hergenrother, P.J.
    ACS Infect. Dis. 2021, 7, 493-505

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  1. 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. 2015, 6, 6947.

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  1. 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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  1. 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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  1. 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).

    Link to journal
  1. 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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  1. 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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  1. 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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  1. 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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