Gareth A. Prosser
University of Manchester
Drug resistanceBacterial geneticsAlanine racemaseMycobacterium tuberculosisAntibioticsBiologyAntibiotic resistance
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Publications 2
#1Cesira de Chiara (Francis Crick Institute)H-Index: 10
#2Miha Homšak (Imperial College London)
Last. Luiz Pedro S. de Carvalho (Francis Crick Institute)H-Index: 11
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The broad-spectrum antibiotic d-cycloserine (DCS) is a key component of regimens used to treat multi- and extensively drug-resistant tuberculosis. DCS, a structural analog of d-alanine, binds to and inactivates two essential enzymes involved in peptidoglycan biosynthesis, alanine racemase (Alr) and d-Ala:d-Ala ligase. Inactivation of Alr is thought to proceed via a mechanism-based irreversible route, forming an adduct with the pyridoxal 5′-phosphate cofactor, leading to bacterial death. Inconsis...
#1Dimitrios Evangelopoulos (Francis Crick Institute)H-Index: 2
#2Gareth A. Prosser (University of Manchester)H-Index: 1
Last. Luiz Pedro S. de Carvalho (Francis Crick Institute)H-Index: 2
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Drug resistant infections represent one of the most challenging medical problems of our time. D-cycloserine is an antibiotic used for six decades without significant appearance and dissemination of antibiotic resistant strains, making it an ideal model compound to understand what drives resistance evasion. We therefore investigated why Mycobacterium tuberculosis fails to become resistant to D-cycloserine. To address this question, we employed a combination of bacterial genetics, genomics, bioche...