ABC-F proteins mediate antibiotic resistance through ribosomal protection

Members of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to an in vitro translation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosome in vitro. To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection

Target protection as a key antibiotic resistance mechanism

Antibiotic resistance is mediated through several distinct mechanisms, most of which are relatively well understood and the clinical importance of which has long been recognized. Until very recently, neither of these statements was readily applicable to the class of resistance mechanism known as target protection, a phenomenon whereby a resistance protein physically associates with an antibiotic target to rescue it from antibiotic-mediated inhibition. In this Review, we summarize recent progress in understanding the nature and importance of target protection. In particular, we describe the molecular basis of the known target protection systems, emphasizing that target protection does not involve a single, uniform mechanism but is instead brought about in several mechanistically distinct ways

Metallica and Morality: The Rhetorical Battleground of the Napster Wars

This article discusses the rhetoric of the highly publicised Napster legal cases, arguing that it is firmly based in the aesthetic and moral implications of copyright infringement. To contextualise current trends historically, the paper summarises insights from recent work analysing the importance of Romanticism to an understanding of contemporary copyright practice. Utilising this theoretical background, the article highlights the importance of the Romantic separation of art and commerce for the recording industry’s anti-piracy campaigns. This enables the industry to centre current rhetoric concerning Napster on artists rather than on commercial interests. This turns copyright infringement into not only an aesthetic crime, but also into a moral one. The article argues that the only way the recording industry can prevent substantial online piracy is by creating and winning a moral argument. However, it concludes that the industry is currently unsuccessful in this aim and offers some reasons for this, themselves predicated upon the Romantic separation of art and market