First dose of cationic dendrimers determines the development of resistance or sensitivity to nanomaterials and antibiotics simultaneously in Pseudomonas aeruginosa.

Cationic dendrimers are considered among the most promising antibacterial agents, whose mechanism of action involves destabilizing the outer membrane of Gram-negative bacteria. Despite being considered an alternative to antibiotics, these systems can lose their effectiveness with prolonged use. Although bacterial resistance to metal nanoparticles is widely discussed, the possible development of resistance to dendrimers has not been investigated. In this article, we report that Pseudomonas aeruginosa PAO1 can develop resistance to carbosilane dendrimers after repeated exposure. Resistance results from changes occurring on the bacterial membrane surface, leading to changes in membrane permeability. Initially, low doses of dendrimers induce resistance to both dendrimers and polymyxin-B. On the other hand, initial high doses do not induce resistance, while increasing susceptibility to chloramphenicol. Long-term use of dendrimers may therefore be associated with the risk of developing resistance to dendrimers and antibiotics, although immediate use of a high dose may eliminate this phenomenon.