How to fight bacteria without inducing drug resistance

The antimicrobial resistance crisis is a serious health issue brought on by the drying up of the antibiotic discovery pipeline and the increase and spread of multi-drug resistant pathogens. The discovery of novel antibiotics with new mechanisms of action proved to be extremely difficult and when discovered, the reservoir of resistance genes in environmental bacteria is making the lifespan of newly introduced drugs extremely short. Resistance to antimicrobial drugs seems mainly driven by the fact that traditional antibiotics are administered in monotherapy and target bacterial essential processes. In this scenario, it would be desirable to shift discovery efforts also to alternative therapeutic strategies with low evolutionary pressure. Antibiotic adjuvants and narrow spectrum therapeutics that target bacterial pathogenesis may offer a solution to this problem. In this chapter, we discuss selected examples of combinatorial therapies as well as anti-virulence strategies targeting well-known virulence structures and pathways.