Affiliation: McMaster University
- Wright G. Mechanisms of resistance to antibiotics. Curr Opin Chem Biol. 2003;7:563-9 pubmed
- 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. ..
- Koteva K, King A, Capretta A, Wright G. Total Synthesis and Activity of the Metallo-Î²-lactamase Inhibitor Aspergillomarasmineâ€…A. Angew Chem Int Ed Engl. 2016;55:2210-2 pubmed publisher..Herein we report the synthesis of aspergillomarasmineâ€…A. The synthesis enabled confirmation of the stereochemical configuration of the compound and offers a route for the synthesis of derivatives in the future. ..
- 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. ..
- ..Avibactam blocks ?-lactamases (?-L) in the periplasm, which would otherwise inactivate the antibiotics resulting in drug resistance. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- ..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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..