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:


             Compound update 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, in press published on web November 24, 2020


             Link to journal


              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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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 20205, 67-75

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Behind the paper


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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Going on offense against the Gram-negative defense

Drown, B.S. and Hergenrother, P. J.

Proc Natl. Acad. Sci. 2018, 115, 6530-6532.

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Broad-Spectrum Antibiotics, a Call for Chemists

Richter, M. F.; Hergenrother, P. J.

Chem 2017, 3, 10-13 (essay).


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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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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

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