Gerard Wright

Summary

Affiliation: McMaster University
Country: Canada

Publications

  1. request reprint
    Wright G. Biochemistry. A new target for antibiotic development. Science. 2007;315:1373-4 pubmed
  2. Tyers M, Wright G. Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nat Rev Microbiol. 2019;17:141-155 pubmed publisher
    ..In this Review, we outline a theoretical and practical framework for the development of effective antibiotic combinations. ..
  3. Xu M, Wright G. Heterologous expression-facilitated natural products' discovery in actinomycetes. J Ind Microbiol Biotechnol. 2019;46:415-431 pubmed publisher
  4. Yim G, Wang W, Pawlowski A, Wright G. Trichlorination of a Teicoplanin-Type Glycopeptide Antibiotic by the Halogenase StaI Evades Resistance. Antimicrob Agents Chemother. 2018;62: pubmed publisher
    ..These results provide insight into the biosynthesis of GPAs and the biological function of GPA chlorination for this medically important class of antibiotic. ..
  5. Morar M, Bhullar K, Hughes D, Junop M, Wright G. Structure and mechanism of the lincosamide antibiotic adenylyltransferase LinB. Structure. 2009;17:1649-1659 pubmed publisher
    ..The LinB structure provides an evolutionary link to ancient nucleotide polymerases and suggests that, like protein kinases and acetyltransferases, these are proto-resistance elements from which drug resistance can evolve. ..
  6. Guitor A, Wright G. Antimicrobial Resistance and Respiratory Infections. Chest. 2018;154:1202-1212 pubmed publisher
  7. Perry J, Westman E, Wright G. The antibiotic resistome: what's new?. Curr Opin Microbiol. 2014;21:45-50 pubmed publisher
    ..Observing the trends and prevalence of genes within the antibiotic resistome is key to maintaining the efficacy of antibiotics in the clinic. ..
  8. Thaker M, Kalan L, Waglechner N, Eshaghi A, Patel S, Poutanen S, et al. Vancomycin-variable enterococci can give rise to constitutive resistance during antibiotic therapy. Antimicrob Agents Chemother. 2015;59:1405-10 pubmed publisher
    ..These VVE strains therefore pose a new challenge to the current regimen of diagnostic tests used for VRE detection in the clinic setting. ..
  9. Cox G, Stogios P, Savchenko A, Wright G. Structural and molecular basis for resistance to aminoglycoside antibiotics by the adenylyltransferase ANT(2″)-Ia. MBio. 2015;6: pubmed publisher
    ..Combined, these findings provide the groundwork for the development of broad-spectrum inhibitors against antibiotic nucleotidyltransferases. ..

More Information

Publications30

  1. request reprint
    Wright G. Mechanisms of resistance to antibiotics. Curr Opin Chem Biol. 2003;7:563-9 pubmed
  2. Cox G, Sieron A, King A, de Pascale G, Pawlowski A, Koteva K, et al. A Common Platform for Antibiotic Dereplication and Adjuvant Discovery. Cell Chem Biol. 2017;24:98-109 pubmed publisher
    ..In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis. ..
  3. Pawlowski A, Johnson J, Wright G. Evolving medicinal chemistry strategies in antibiotic discovery. Curr Opin Biotechnol. 2016;42:108-117 pubmed publisher
  4. Koteva K, King A, Capretta A, Wright G. Total Synthesis and Activity of the Metallo-β-lactamase Inhibitor Aspergillomarasmine A. Angew Chem Int Ed Engl. 2016;55:2210-2 pubmed publisher
    ..Herein we report the synthesis of aspergillomarasmine A. The synthesis enabled confirmation of the stereochemical configuration of the compound and offers a route for the synthesis of derivatives in the future. ..
  5. Wright G. Q&A: antibiotic resistance: what more do we know and what more can we do?. BMC Biol. 2013;11:51 pubmed publisher
  6. Robbins N, Spitzer M, Yu T, Cerone R, Averette A, Bahn Y, et al. An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity against Diverse Fungal Pathogens. Cell Rep. 2015;13:1481-1492 pubmed publisher
    ..Thus, the ACM is a rich reservoir of chemical combinations with therapeutic potential against diverse fungal pathogens. ..
  7. Wright G. Q&A: Antibiotic resistance: where does it come from and what can we do about it?. BMC Biol. 2010;8:123 pubmed publisher
  8. Albu S, Koteva K, King A, Al Karmi S, Wright G, Capretta A. Total Synthesis of Aspergillomarasmine?A and Related Compounds: A Sulfamidate Approach Enables Exploration of Structure-Activity Relationships. Angew Chem Int Ed Engl. 2016;55:13259-13262 pubmed publisher
  9. Wright G. Empowering Older Antibiotics. Cell. 2016;167:301 pubmed publisher
    ..Avibactam blocks ?-lactamases (?-L) in the periplasm, which would otherwise inactivate the antibiotics resulting in drug resistance. ..
  10. Cox G, Koteva K, Wright G. An unusual class of anthracyclines potentiate Gram-positive antibiotics in intrinsically resistant Gram-negative bacteria. J Antimicrob Chemother. 2014;69:1844-55 pubmed publisher
    ..This result demonstrates the great potential of this approach in expanding antibiotic effectiveness in the face of the growing challenge of resistance in Gram-negatives. ..
  11. Koteva K, Cox G, Kelso J, Surette M, Zubyk H, Ejim L, et al. Rox, a Rifamycin Resistance Enzyme with an Unprecedented Mechanism of Action. Cell Chem Biol. 2018;25:403-412.e5 pubmed publisher
    ..This unique mechanism of enzymatic inactivation underpins the broad spectrum of rifamycin resistance mediated by Rox enzymes and presents a new antibiotic resistance mechanism not yet seen in microbial antibiotic detoxification. ..
  12. Pawlowski A, Westman E, Koteva K, Waglechner N, Wright G. The complex resistomes of Paenibacillaceae reflect diverse antibiotic chemical ecologies. ISME J. 2018;12:885-897 pubmed publisher
    ..We find that in contrast to pathogens, mobile genetic elements are not significantly responsible for resistome remodeling. This offers divergent modes of resistome development in pathogens and environmental bacteria. ..
  13. Pawlowski A, Stogios P, Koteva K, Skarina T, Evdokimova E, Savchenko A, et al. The evolution of substrate discrimination in macrolide antibiotic resistance enzymes. Nat Commun. 2018;9:112 pubmed publisher
    ..This approach should be applicable for studying the functional evolution of any antibiotic resistance enzyme and for evaluating the evolvability of resistance enzymes to new generations of antibiotic scaffolds. ..
  14. Waglechner N, Wright G. Antibiotic resistance: it's bad, but why isn't it worse?. BMC Biol. 2017;15:84 pubmed publisher
    ..This is highly relevant to understanding the emergence of resistance in pathogenic bacteria that can inform better antibiotic management practices and influence new drug discovery. ..
  15. request reprint
    Wright G. On the road to bacterial cell death. Cell. 2007;130:781-3 pubmed
    ..In this issue, Kohanski et al. (2007) provide evidence that the production of reactive oxygen species is a shared mechanism of cell death initiated by bactericidal antibiotics. ..
  16. Wright G. Antibiotics: a new hope. Chem Biol. 2012;19:3-10 pubmed publisher
    ..This knowledge is fueling a renaissance of interest and innovation in antibiotic discovery, synthesis, and mechanism that is poised to inform drug discovery to address pressing clinical needs. ..
  17. Rotondo C, Wright G. Inhibitors of metallo-?-lactamases. Curr Opin Microbiol. 2017;39:96-105 pubmed publisher
    ..While none of these inhibitors are yet in human clinical trials, the increasing importance of these enzymes in drug failure is a strong incentive to continue identifying and characterizing such molecules. ..
  18. Wright G. Opportunities for natural products in 21st century antibiotic discovery. Nat Prod Rep. 2017;34:694-701 pubmed publisher
    ..Natural product research is poised to regain prominence in delivering new drugs to solve the antibiotic crisis. ..
  19. Robbins N, Spitzer M, Wang W, Waglechner N, Patel D, O Brien J, et al. Discovery of Ibomycin, a Complex Macrolactone that Exerts Antifungal Activity by Impeding Endocytic Trafficking and Membrane Function. Cell Chem Biol. 2016;23:1383-1394 pubmed publisher
  20. Wright G. Antibiotic Adjuvants: Rescuing Antibiotics from Resistance. Trends Microbiol. 2016;24:862-871 pubmed publisher
    ..Adjuvants offer a means to both suppress the emergence of resistance and rescue the activity of existing drugs, offering an orthogonal strategy complimentary to new antibiotic discovery VIDEO ABSTRACT. ..
  21. Spanogiannopoulos P, Waglechner N, Koteva K, Wright G. A rifamycin inactivating phosphotransferase family shared by environmental and pathogenic bacteria. Proc Natl Acad Sci U S A. 2014;111:7102-7 pubmed publisher
    ..This work identifies a new antibiotic resistance protein family and reinforces the fact that the study of resistance in environmental organisms can serve to identify resistance elements with relevance to pathogens. ..