Identification of biocides with limited resistance in bacterial pathogens

Biocides, common antibacterial agents in food and cosmetics, have raised concerns about potentially promoting antibiotic resistance. Here we focus on resistance against 16 biocides in three important bacterial pathogens. We found several biocides with low susceptibility to resistance by mutations and with scarce occurrence of mobile resistance genes in human-related microbiomes. In addition, the identified biocide resistance mechanisms typically provide low resistance levels only and diminish bacterial virulence in an invertebrate infection model. Finally, analysis of multidrug-resistant clinical isolates revealed that cross-resistance between biocides and clinically relevant antibiotics is uncommon. Alarmingly, however, triclosan resistance leads to cross-resistance with an antibiotic in clinical development. These results could explain why resistance to certain biocides is rare in the environment despite widespread human usage. The findings could aid in establishing guidelines for biocide applications and contribute to the development of resistance-proof antibiotics.