Program in Antimicrobial Resistance and Drug Discovery

The Program in Antimicrobial Resistance and Drug Discovery is focused on tackling the third leading cause of death due to infectious disease worldwide - antibiotic resistant bacteria.

Program Goals:

  • Advance understanding on how existing antimicrobials act and define the mechanisms of bacterial drug resistance and drug tolerance through basic experimental research. 
  • Partner with clinicians and public health labs to expand the ability to monitor and identify emerging antibiotic resistance threats

Recent Publications

  • Todd RT, Soisangwan N, Peters S, Kemp B, Crooks T, Gerstein A, Selmecki A. Antifungal drug concentration impacts the spectrum of adaptive mutations in Candida albicans. Mol Biol Evol. 2023;40(1):msad009. doi: 10.1093/molbev/msad009 

  • Sullivan MR, McGowen K, Liu Q, Akusobi C, Young DC, Mayfield JA, Raman S, Wolf ID, Moody DB, Aldrich CC, Muir A, Rubin EJ. Biotin-dependent cell envelope remodelling is required for Mycobacterium abscessus survival in lung infection. Nat Microbiol. 2023;8(3):481-497. doi: 10.1038/s41564-022-01307-5
  • Berg K, Hegde P, Pujari V, Brinkmann M, Wilkins DZ, Parish T, Crick DC, Aldrich CC. SAR study of piperidine derivatives as inhibitors of 1,4-dihydroxy-2-naphthoate isoprenyltransferase (MenA) from Mycobacterium tuberculosis. Eur J Med Chem. 2023;249:115125. doi: 10.1016/j.ejmech.2023.115125 
  • Nandula, SR, Kondeti, VSSK, Phan, C, Wang, J, Penningroth, MR, Granick, JL, Bruggeman, PJ, Hunter, RC, Plasma-induced inactivation of Staphylococcus aureus biofilms: The role of atomic oxygen and comparison with disinfectants and antibiotics. Plasma Process Polym. 2023;20:e2200147 doi: 10.1002/ppap.202200147
  • Wenzler E, Maximos M, Asempa TE, Biehle L, Schuetz AN, Hirsch EB. Antimicrobial susceptibility testing: An updated primer for clinicians in the era of antimicrobial resistance: Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2023;00:1-15. doi: 10.1002/phar.2781
  • Gaire TN, Scott HM, Noyes NR, Ericsson AC, Tokach MD, Menegat MB, Vinasco J, Roenne B, Ray T, Nagaraja TG, Volkova VV. Age influences the temporal dynamics of microbiome and antimicrobial resistance genes among fecal bacteria in a cohort of production pigs. Anim Microbiome. 2023;5(1):2. doi: 10.1186/s42523-022-00222-8
  • Bonin N, Doster E, Worley H, Pinnell LJ, Bravo JE, Ferm P, Marini S, Prosperi M, Noyes N, Morley PS, Boucher C. MEGARes and AMR++, v3.0: an updated comprehensive database of antimicrobial resistance determinants and an improved software pipeline for classification using high-throughput sequencing. Nucleic Acids Res. 2023;51(D1):D744-D752. doi: 10.1093/nar/gkac1047
  • Belofsky G, Ahn H, Zapata M, Wilcox D, Salomon CE, Spiegel PC. Antimicrobial isoflavans and other metabolites of Dalea jamesii. Planta Med. 2023;89:1-10. doi: 10.1055/a-2013-3008
  • Marshall AP, Carlson EE. Metabolomics Reveals a "Trimeric" γ-Actinorhodin from Streptomyces coelicolor M145. ChemBioChem. 2023;(24):e202200757. doi: 10.1002/cbic.202200757 
  • Cole MS, Howe MD, Buonomo JA, Sharma S, Lamont EA, Brody SI, Mishra NK, Minato Y, Thiede JM, Baughn AD, Aldrich CC. Cephem-Pyrazinoic Acid Conjugates: Circumventing resistance in Mycobacterium tuberculosis. Chemistry. 2022;28(51):e202200995. doi: 10.1002/chem.202200995
  • Hegde PV, Howe MD, Zimmerman MD, Boshoff HIM, Sharma S, Remache B, Jia Z, Pan Y, Baughn AD, Dartois V, Aldrich CC. Synthesis and biological evaluation of orally active prodrugs and analogs of para-aminosalicylic acid (PAS). Eur J Med Chem. 2022;232:114201. doi: 10.1016/j.ejmech.2022.114201
  • Green KD, Pang AH, Thamban Chandrika N, Garzan A, Baughn AD, Tsodikov OV, Garneau-Tsodikova S. Discovery and optimization of 6-(1-substituted pyrrole-2-yl)-s-triazine containing compounds as antibacterial agents. ACS Infect Dis. 2022;8(4):757-767. doi: 10.1021/acsinfecdis.1c00450
  • Bollig ER, Hirsch EB, Bueno I, Lynfield R, Granick JL, Gens KD, Rashid A, Harris K, Boeser K, Beaudoin AL. Minnesota One Health Antibiotic Stewardship Collaborative: A reproducible approach to facilitate antimicrobial stewardship progress. Open Forum Infect Dis. 2022;9(12):ofac602. doi: 10.1093/ofid/ofac602
  • Fletcher JR, Villareal AR, Penningroth MR, Hunter RC. Staphylococcus aureus overcomes anaerobe-derived short-chain fatty acid stress via FadX and the CodY regulon. J Bacteriol. 2022;204(5):e0006422. doi: 10.1128/jb.00064-22 
  • Ottesen A, Kocurek B, Ramachandran P, Reed E, Commichaux S, Engelbach, G. Mammel, M, Saint Fleurant, S,; Zhao, S, Kabera, C, Merrill, A, Bonin, N, Worley, H, Noyes, N, Boucher, C, McDermott, P, Strain, E. Advancing antimicrobial resistance monitoring in surface waters with metagenomic and quasimetagenomic methods. PLOS Water 2022;1(12): e0000067 doi: 10.1371/journal.pwat.0000067
  • Gaire, T.N., Odland, C., Zhang, B. et al. The impacts of viral infection and subsequent antimicrobials on the microbiome-resistome of growing pigs. Microbiome 2022;10:118. doi: 10.1186/s40168-022-01312-0
  • Ray T, Gaire TN, Dean CJ, Rowe S, Godden SM, Noyes NR. The microbiome of common bedding materials before and after use on commercial dairy farms. Anim Microbiome 2022;4(1):18. doi: 10.1186/s42523-022-00171-2 
  • Rizzo M, Soisangwan N, Vega-Estevez S, Price RJ, Uyl C, Iracane E, Shaw M, Soetaert J, Selmecki A, Buscaino A. Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process. PLoS Genet. 2022;18(12):e1010576. doi: 10.1371/journal.pgen.1010576. 
  • Burrack LS, Todd RT, Soisangwan N, Wiederhold NP, Selmecki A. Genomic diversity across Candida auris clinical isolates shapes rapid development of antifungal resistance In vitro and In vivo. mBio 2022;13(4):e0084222. doi: 10.1128/mbio.00842-22
  • Flanders PL, Contreras-Martel C, Brown NW, Shirley JD, Martins A, Nauta KN, Dessen A, Carlson EE, Ambrose EA. Combined structural analysis and molecular dynamics reveal penicillin-binding protein inhibition mode with β-lactones. ACS Chem Biol. 2022;17(11):3110-3120. doi: 10.1021/acschembio.2c00503
  • Shirley JD, Nauta KM, Carlson EE. Live-cell profiling of penicillin-binding protein inhibitors in Escherichia coli MG1655. ACS Infect Dis. 2022;8(7):1241-1252. doi: 10.1021/acsinfecdis.2c00004
  • Willett JLE, Robertson EB, Dunny GM. The phosphatase Bph and peptidyl-prolyl isomerase PrsA are required for gelatinase expression and activity in Enterococcus faecalis. J Bacteriol. 2022;204(7):e0012922. doi: 10.1128/jb.00129-22
  • Edwin Erayil S, Palzer E, Kline S. An evaluation of risk factors for Staphylococcus aureus colonization in a pre-surgical population. Access Microbiol. 2022;4(1):000316. doi: 10.1099/acmi.0.000316
  • Perfect JR, Krysan DJ, Del Poeta M, Selmecki AM, Brown JCS, Cowen LE. Editorial: Antifungal pipeline: Build it strong; build it better! Front Cell Infect Microbiol. 2022;12:881272. doi: 10.3389/fcimb.2022.881272
  • Lassinantti L, Camacho MI, Erickson RJB, Willett JLE, De Lay NR, Ter Beek J, Dunny GM, Christie PJ, Berntsson RP. Enterococcal PrgU Provides additional regulation of pheromone-inducible conjugative plasmids. Bacteriology 2021;6(3):e0026421. doi: 10.1128/mSphere.00264-21
  • Thiede JM, Dillon NA, Howe MD, Aflakpui R, Modlin SJ, Hoffner SE, Valafar F, Minato Y, Baughn AD. Pyrazinamide susceptibility is driven by activation of the SigE-Dependent Cell Envelope Stress Response in Mycobacterium tuberculosis. mBio. 2021;13(1):e0043921. doi: 10.1128/mbio.00439-21 
  • Modlin SJ, Elghraoui A, Gunasekaran D, Zlotnicki AM, Dillon NA, Dhillon N, Kuo N, Robinhold C, Chan CK, Baughn AD, Valafar F. Structure-aware Mycobacterium tuberculosis functional annotation uncloaks resistance, metabolic, and virulence genes. mSystems 2021;6(6):e0067321. doi: 10.1128/mSystems.00673-21
  • Lucas SK, Villarreal AR, Ahmad MM, Itabiyi A, Feddema E, Boyer HC, Hunter RC. Anaerobic microbiota derived from the upper airways impact Staphylococcus aureus physiology. Infect Immun. 2021;89(9):e0015321. doi: 10.1128/IAI.00153-21
  • Hegde P, Boshoff HIM, Rusman Y, Aragaw WW, Salomon CE, Dick T, Aldrich CC. Reinvestigation of the structure-activity relationships of isoniazid. Tuberculosis. 2021;129:102100. doi: 10.1016/j.tube.2021.102100
  • MacAlpine J, Daniel-Ivad M, Liu Z, Yano J, Revie NM, Todd RT, Stogios PJ, Sanchez H, O'Meara TR, Tompkins TA, Savchenko A, Selmecki A, Veri AO, Andes DR, Fidel PL Jr, Robbins N, Nodwell J, Whitesell L, Cowen LE. A small molecule produced by Lactobacillus species blocks Candida albicans filamentation by inhibiting a DYRK1-family kinase. Nat Commun. 2021;12(1):6151. doi: 10.1038/s41467-021-26390-w