Novel Gram-Negative Antibiotics

Multidrug-resistant Gram-negative infections are dramatically on the rise as there has not been a novel class of antibiotics approved for these pathogens since 1968.  We have been working to develop rules that can predict the types of compounds that are able to accumulate in Gram-negative bacteria, and we have recently published these rules and have applied them to convert the Gram-positive-only natural product antibiotic DNM into a version that also kills Gram-negative bacteria.


Related Publications:

  1. Rationalizing generation of broad spectrum antibiotics with the addition of a positive charge
    Haloi, N.; Vasan, A.K.; Geddes, E.; Prasanna, A.; Wen, P.-C.; Metcalf, W.W.; Hergenrother, P.J.; Tajkhorshid, E.
    Chem. Sci. 2021, in press published on web October 14, 2021

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  1. A LC-MS/MS assay and complementary web-based tool to quantify and predict compound accumulation in E. coli
    Geddes, E.J; Li, Z.; Hergenrother, P.J.
    Nature Protocols 2021, in press published on web September 3, 2021

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  1. Facilitating compound entry as a means to discover antibiotics for Gram-negative bacteria
    Munoz, K.A. and Hergenrother, P.J.
    Acc. Chem. Res. 202154, 1322-1333

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  1. Compound uptake into E. coli can be facilitated by N-alkyl guanidiniums and pyridinium
    Perlmutter, S.J.; Geddes, E.J.; Drown, B.S.; Motika, S.E.; Lee, M.R.; Hergenrother, P.J.  
    ACS Infect. Dis., 2020, 7, 162-173

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  1. A Gram-Negative Antibiotic Active Through Inhibition of an Essential Riboswitch
    Motika, S. E; Ulrich, R. J.; Geddes, E. J.; Lee, H. Y.; Lau, G. W.; Hergenrother, P. J.
    J. Am. Chem. Soc. 2020142, 10856-10862

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  1. Implementation of permeation rules leads to a FabI inhibitor with activity against Gram-negative pathogens
    Parker, E. N.; Drown, B. S.; Geddes, E. J.; Lee, H.-Y.; Ismail, N.; Lau, G. W. and Hergenrother, P. J.
    Nature Microbiology 2020, 5, 67-75

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    UIUC press release
    Behind the paper

  1. The challenge of converting Gram-positive-only compounds into broad-spectrum antibiotics
    Richter, M. F. and Hergenrother, P. J.
    Ann NY Acad Sci. 2019, 1435, 18-38.

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  1. Going on offense against the Gram-negative defense
    Drown, B.S. and Hergenrother, P. J.
    Proc Natl. Acad. Sci. 2018115, 6530-6532.

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  1. Broad-Spectrum Antibiotics, a Call for Chemists
    Richter, M. F.; Hergenrother, P. J.
    Chem 20173, 10-13 (essay).

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  1. Predictive Compound Accumulation Rules Yield a Broad-Spectrum Antibiotic
    Richter, M. F.; Drown, B. S.; Riley, A. P.; Garcia, A.; Shirai, T.; Svec, R. L.; Hergenrother, P. J. 
    Nature 2017, 545, 299-304.

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    UIUC press release
    ScienceNews highlight
    Nature Microbiology blog
    C&E News story
    Antibiotics – The Perfect Storm blog
    American Council on Science & Health story
    Biotechniques highlight
    Nature Biotechnology highlight
    Cell Chemical Biology highlight