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Positive epistasis drives the acquisition of multidrug resistance

2009-07Journal article Open access
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dc.contributor.authorTrindade, S.
dc.contributor.authorSousa, A.
dc.contributor.authorXavier, K.B.
dc.contributor.authorDionísio, F.
dc.contributor.authorFerreira, M.G.
dc.contributor.authorGordo, I.
dc.date.accessioned2009-09-29T16:56:44Z
dc.date.available2009-09-29T16:56:44Z
dc.date.issued2009-07
dc.description.abstractThe 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. Surprisingly we find that a significant fraction of resistant mutations can be beneficial in certain resistant genetic backgrounds, that some double resistances entail no measurable cost, and that some allelic combinations are hotspots for rapid compensation. These results provide additional insight as to why multi-resistant bacteria are so prevalent and reveal an extra layer of complexity on epistatic patterns previously unrecognized, since it is hidden in genome-wide studies of genetic interactions using gene knockoutspt
dc.identifier.citationTrindade S, Sousa A, Xavier KB, Dionisio F, Ferreira MG, Gordo I. (2009). "Positive epistasis drives the acquisition of multidrug resistance".Plos Genetics. 5(7): e1000578pt
dc.identifier.doihttps://doi.org/10.1371/journal.pgen.1000578
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/10400.7/32
dc.language.isoengpt
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pgen.1000578
dc.subjectEpistasis, Geneticpt
dc.subjectEvolution, Molecularpt
dc.subjectDrug Resistance, Multiple, Bacterialpt
dc.titlePositive epistasis drives the acquisition of multidrug resistancept
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPagee1000578pt
oaire.citation.titlePlos Geneticspt
rcaap.rightsopenAccesspt
rcaap.typearticlept

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