@article{barker_martin_chandler_nguyen_harris_goodell_melander_doi_ernst_melander_2017, title={Small molecule adjuvants that suppress both chromosomal and mcr-1 encoded colistin-resistance and amplify colistin efficacy in polymyxin-susceptible bacteria}, volume={25}, ISSN={["1464-3391"]}, DOI={10.1016/j.bmc.2017.08.055}, abstractNote={Bacterial resistance to polymyxin antibiotics has taken on a new and more menacing form. Common are genomically-encoded resistance mechanisms to polymyxins, specifically colistin (polymyxin E), however, the plasmid-borne mobile colistin resistance-1 (mcr-1) gene has recently been identified and poses a new threat to global public health. Within six months of initial identification in Chinese swine in November 2015, the first human clinical isolation in the US was reported (Apr. 2016). Herein we report successful reversion of mcr-1-driven colistin resistance in Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli with adjuvants we previously reported as modulators of chromosomally-encoded colistin resistance. Further screening of our in-house library of nitrogen-dense heterocycles has identified additional chemical scaffolds that actively attenuate colistin resistance. Ultimately, we present a diverse cohort of adjuvants that both sensitize colistin-resistant and colistin-susceptible bacteria to this antibiotic, thus providing a potential avenue to both reduce colistin dosage and toxicity, and overcome colistin resistance.}, number={20}, journal={BIOORGANIC & MEDICINAL CHEMISTRY}, author={Barker, William T. and Martin, Sara E. and Chandler, Courtney E. and Nguyen, T. Vu. and Harris, Tyler L. and Goodell, Christopher and Melander, Roberta J. and Doi, Yohei and Ernst, Robert K. and Melander, Christian}, year={2017}, month={Oct}, pages={5749–5753} }
 @article{garrido_simpson_dahl_bresee_whitehead_lindsey_harris_smith_carter_feldheim_et al._2015, title={Gold nanoparticles to improve HIV drug delivery}, volume={7}, ISSN={["1756-8927"]}, DOI={10.4155/fmc.15.57}, abstractNote={ Background: Antiretroviral therapy (ART) has improved lifespan and quality of life of patients infected with the HIV-1. However, ART has several potential limitations, including the development of drug resistance and suboptimal penetration to selected anatomic compartments. Improving the delivery of antiretroviral molecules could overcome several of the limitations of current ART. Results & Conclusion: Two to ten nanometer diameter inorganic gold crystals serve as a base scaffold to combine molecules with an array of properties in its surface. We show entry into different cell types, antiviral activity of an HIV integrase inhibitor conjugated in a gold nanoparticle and penetration into the brain in vivo without toxicity. Herein, gold nanoparticles prove to be a promising tool to use in HIV therapy. }, number={9}, journal={FUTURE MEDICINAL CHEMISTRY}, author={Garrido, Carolina and Simpson, Carrie A. and Dahl, Noelle P. and Bresee, Jamee and Whitehead, Daniel C. and Lindsey, Erick A. and Harris, Tyler L. and Smith, Candice A. and Carter, Carly J. and Feldheim, Daniel L. and et al.}, year={2015}, pages={1097–1107} }
 @article{harris_worthington_hittle_zurawski_ernst_melander_2014, title={Small Molecule Downregulation of PmrAB Reverses Lipid A Modification and Breaks Colistin Resistance}, volume={9}, ISSN={["1554-8937"]}, DOI={10.1021/cb400490k}, abstractNote={Infections caused by multi-drug resistant bacteria, particularly Gram-negative bacteria, are an ever-increasing problem. While the development of new antibiotics remains one option in the fight against bacteria that have become resistant to currently available antibiotics, an attractive alternative is the development of adjuvant therapeutics that restore the efficacy of existing antibiotics. We report a small molecule adjuvant that suppresses colistin resistance in multidrug resistant Acinetobacter baumannii and Klebsiella pneumoniae by interfering with the expression of a two-component system. The compound downregulates the pmrCAB operon and reverses phosphoethanolamine modification of lipid A responsible for colistin resistance. Furthermore, colistin-susceptible and colistin-resistant bacteria do not evolve resistance to combination treatment. This represents the first definitive example of a compound that breaks antibiotic resistance by directly modulating two-component system activity.}, number={1}, journal={ACS CHEMICAL BIOLOGY}, author={Harris, Tyler L. and Worthington, Roberta J. and Hittle, Lauren E. and Zurawski, Daniel V. and Ernst, Robert K. and Melander, Christian}, year={2014}, month={Jan}, pages={122–127} }
 @article{harris_worthington_melander_2012, title={Potent Small-Molecule Suppression of Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus}, volume={51}, ISSN={["1521-3773"]}, DOI={10.1002/anie.201206911}, abstractNote={Shields down! Adjuvant molecules that have the ability to restore the susceptibility of multi-drug-resistant bacteria, such as MRSA, to clinically available antibiotics are a promising alternative to the development of novel antimicrobials. Pictured is a potent small molecule (1) that, at sub-minimum inhibitory concentration (sub-MIC) levels, lowers the MIC of oxacillin (2) against a number of MRSA strains by up to 512-fold.}, number={45}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Harris, Tyler L. and Worthington, Roberta J. and Melander, Christian}, year={2012}, pages={11254–11257} }