Positive Epistasis Drives the Acquisition of Multidrug Resistance

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.

Investigation of trypanothione synthetase of Leishmania infantum as a potential target for new anti-parasitic drugs

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate

Dissertação para obtenção do Grau de Mestre em Biotecnologia

User friendly knowledge acquisition system for medical devices actuation

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Compositional and functional analysis of polycomb target chromatin

Dissertation presented to obtain the Ph.D degree in Molecular Biology

Insights into cell wall synthesis and cell division in Staphylococcus aureus

Dissertation presented to obtain the Ph.D degree in Biology

Marketing plan for Snack Books

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Corporate social responsibility and its effect on image and reputation: The case of L’Oréal and its acquisition of The Body Shop

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Evaluation of the impact of L’Oréal’s acquisition of The Body Shop on both brands

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Acquisition of Plus Discount by Jerónimo Martins

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics

Acquisition of Carrefour-Portugal by Sonae Distribuição

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Acquisition of Horizon Wind Energy by EdP

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics

Dependence of IVIM-DWI estimations on acquisition parameters

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Interactive acquisition of spatial information from images for multimedia applications

Dissertação para obtenção do Grau de Doutor em Informática

Target-specific multiphysics modeling for thermal medicine applications

Dissertation to obtain the degree of Doctor of Philosophy in Biomedical Engineering