Content area
Full Text
REVIEWS
Molecular mechanisms of antibiotic resistance
Jessica M.A. Blair*, Mark A. Webber*, Alison J. Baylay, David O. Ogbolu and Laura J.V. Piddock
Abstract | Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
Antibiotics underpin modern medicine; their use has reduced childhood mortality and increased life expectancy, and they are crucial for invasive surgery and treatments such as chemotherapy. However, the number of infections caused by multidrug-resistant bacteria is increasing globally, and the spectre of untreatable infections is becoming a reality. The most recent World Economic Forum Global Risks reports have listed antibiotic resistance as one of the greatest threats to human health13. It is estimated that in Europe 25,000 people die each year as a result of multidrug-resistant bacterial infections and that this costs the European Union economy 1.5 billion annually1. In the United States more than 2 million people are infected with antibiotic-resistant bacteria annually, with 23,000 deaths as a direct result4,5. In addition to increased resistance to existing agents, there is a lack of new antibiotics in development. The word antibiotic has become synonymous with antibacterial drug: therefore, in this article the term antibiotic has been used throughout.
Bacteria can be intrinsically resistant to certain antibiotics but can also acquire resistance to antibiotics via mutations in chromosomal genes and by horizontal gene transfer. The intrinsic resistance of a bacterial species to a particular antibiotic is the ability to resist the action of that antibiotic as a result of inherent structural or functional characteristics (FIG.1). The simplest example of intrinsic resistance in an individual species results from the absence of a susceptible target of a specific antibiotic; for example, the biocide triclosan has broad efficacy against Gram-positive bacteria and many...