**3.4 Interaction with cell membrane**

Various anthelmintic, anticancer and antiprotozoal drugs such as niclosamide, oxyclozanide, rafoxanide, ivermectin, mitotane, pentamidine and robenidine have been reported to interact with the bacterial cell membrane. Three anthelmintic drugs in combination with colistin have shown activity against GNB by the regulation of electric charges. Niclosamide and rafoxanide were discovered to increase the negative surface charge of bacterial membrane in *A. baumannii* and *K. pneumoniae* clinical strains *in vitro* [30, 47]. In turn, oxyclozanide has enhanced the activity of additional tobramycin against *P. aeruginosa* by reducing the membrane potential and increasing tobramycin accumulation [28]. This increase in the negative surface charges allow to restore the activity of colistin in colistin-resistant (Col-R) *A. baumannii* and *K. pneumoniae*, and the activity tobramycin in tobramycin-resistant *P. aeruginosa* [30, 47]. Not only the regulation of electric charges has been reported as mechanism of action of anthelmintic drugs, but the increase of bacterial membrane permeabilization has also been reported. Oxyclozanide, rafoxanide and ivermectin have been shown to increase the membrane permeability of *A. baumannii*, *P. aeruginosa* and *K. pneumoniae*, especially in Col-R strains [46–48]. Moreover, Tran et al. have demonstrated that mitotane, a FDA-approved antineoplastic drug, in combination of polymyxin B lead mitotane to enter inside *A. baumannii*, *P. aeruginosa* and *K. pneumoniae* through the permeabilization of the outer membrane by polymyxin B [49]. Additionally, antiprotozoal drugs, pentamidine and robenidine, possess a mechanism of action that disturbs the outer membrane of GNB, due to the interaction with membrane lipopolysaccharides (LPS) [29, 50]. Finally, ebselen has also presented antibacterial effect against *A. baumannii* and *E. coli* by inhibiting the TonB-mediated physiology, which is involved in iron acquisition from host sources [51].
