The Neglected Intrinsic Resistome of Bacterial Pathogens

Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature

Predicting antibiotic resistance

The treatment of bacterial infections is increasingly complicated because microorganisms can develop resistance to antimicrobial agents. This article discusses the information that is required to predict when antibiotic resistance is likely to emerge in a bacterial population. Indeed, the development of the conceptual and methodological tools required for this type of prediction represents an important goal for microbiological research. To this end, we propose the establishment of methodological guidelines that will allow researchers to predict the emergence of resistance to a new antibiotic before its clinical introduction.J.L.M. was supported by grants LSHM-CT-2005-518152, LSHM-CT-2005-018705 and BIO2005-04278. F.B. was supported by grants LSHM-CT-2005-518152 and LSHM-CT-2005-018705. D.I.A. was supported by grants from the Swedish Research Council, LSHM-CT-2005-51852 and Uppsala University, Sweden.Peer reviewe