Antibiotics and Resistance: A Fatal Attraction

When penicillin and other classes of antibiotics were discovered and used to treat infectious diseases human morbidity and mortality due to infective microorganisms were successfully contrasted. However, almost as soon as antibacterial drugs were introduced in clinics, bacterial resistance spread. From a biological and microbiological viewpoint, antibacterial drug resistance is a fascinating aspect of molecular evolution, and resistome concept has been introduced to shed light on driving forces that control the spreading and maintenance of resistance genes within microbial populations. Despite the wide range of chemical complexity of antibiotics, there is a restricted number of modes of action and, on the other hand, bacteria may manifest resistance to antibacterial drugs through a restricted range of molecular strategies. In fact, resistant bacteria can possess molecular mechanisms acting on the antibiotic molecular structure and thus inhibiting its effect. On the other hand, antibiotic target can be altered to have low affinity for antibiotic recognition in the resistant bacterium. Finally, when the cellular target of an antibiotic is located inside cells, antibiotic–target interaction can be prevented by pumping the antibiotic out from resistant bacterial cells through efflux pumps to keep low the intracellular drug concentrations. In this chapter, resistance mechanisms are systematically described and discussed with respect to molecular strategies and modes of action. Spreading models are also discussed with highlights on two examples of intrinsic and acquired antibiotic resistance in Pseudomonas aeruginosa and Staphylococcus aureus, respectively.