DSpace UNL

RUN >
Instituto de Tecnologia Química e Biológica (ITQB) >
ITQB R&D Units >
ITQB: Biology >
ITQB: Bacterial Signalling >
ITQB: BS - Artigos em revista internacional com arbitragem científica >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10362/5844

Title: Positive Epistasis Drives the Acquisition of Multidrug Resistance
Authors: Trindade, S
Sousa, A
Xavier, KB
Dionisio, F
Ferreira, MG
Gordo, I
Keywords: antibiotic-resistance, escherichia-coli, mycobacterium-tuberculosis, deleterious mutations, compensatory mutations, fitness costs, evolution, adaptation, bacteria
Issue Date: 1-Jan-2009
Publisher: Public Library of Science (PLoS)
Series/Report no.: Unknown
Abstract: 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. 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 knockouts.
URI: http://hdl.handle.net/10362/5844
ISSN: 1553-7390
Appears in Collections:ITQB: BS - Artigos em revista internacional com arbitragem científica

Files in This Item:

File Description SizeFormat
01325.pdf328.29 kBAdobe PDFView/Open
Statistics
View Statistics
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Universidade Nova de Lisboa  - Statistics  - Feedback
Estamos no RCAAP Governo Português separator Ministério da Educação e Ciência   Fundação para a Ciência e a Tecnologia

Financiado por:

POS_C UE