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Positive Epistasis Drives the Acquisition of Multidrug Resistance

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Detalhes bibliográficos
Resumo:The evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact-epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics.
Autores principais:Trindade, S.
Outros Autores:Sousa, A.; Xavier, KB.; Dionisio, F.; Ferreira, MG.; Gordo, I.
Assunto:ANTIBIOTIC-RESISTANCE ESCHERICHIA-COLI MYCOBACTERIUM-TUBERCULOSIS DELETERIOUS MUTATIONS COMPENSATORY MUTATIONS FITNESS COSTS
Ano:2009
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Repositório do GIMM – Gulbenkian Institute for Molecular Medicine
Idioma:inglês
Origem:ARCA
Descrição
Resumo:The evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact-epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics.