Niclosamide as an antibacterial agent
Niclosamide has well-identified antimicrobial properties and has been shown to prevent the formation of biofilms of hospital-acquired and device associated gram-positive bacteria, such as Staphylococcus aureus (S. aureus) and Methicillin resistant S. aureus (MRSA) at concentrations as low as 0.01μgml-1 (Gwisai et al., 2017). When applied as a device coating, niclosamide prevented bacterial attachment and demonstrated potent antimicrobial activity (Gwisai et al., 2017). In a screen of 1,280 commercially available drugs, niclosamide was one of nine agents that possessed antimicrobial activity against preformed biofilms (Torres et al., 2016). A time-kill study further showed that niclosamide is bacteriostatic against a number of gram-positive bacteria including MRSA, displaying strong in vivoas well as in vitro activity (Rajamuthiah et al., 2015). In a murine model, niclosamide had activities against clinical isolates of vancomycin-resistant Enterococcus faecium (VRE) and was superior to linezolid as a decolonizing agent (Mohammad, AbdelKhalek, Abutaleb, & Seleem, 2018). Tam et al., (2018) showed that niclosamide inhibited the pathogenesis of multi-drug resistant Clostridium difficile(C. difficile) by targeting entry of its toxins into colonocytes. In mice, niclosamide reduced both the primary disease and recurrence, without disrupting the gut microbiota and demonstrated an excellent safety profile. Niclosamide is stable in acidic pH and synergizes with metronidazole and proton pump inhibitors to eliminate Helicobacter pylori (H. pylori) adhesion/invasion via multiple mechanisms such as reducing trans-membrane pH, inhibiting IL-8 secretion and disruptingH. pylori proton motility (Tharmalingam, Port, Castillo, & Mylonakis, 2018). A screen of FDA-approved drugs identified niclosamide as an inhibitor of the Pseudomonas aeruginosa (P. aeruginosa)quorum sensing signaling molecules (Imperi et al., 2013). Finally, niclosamide has significant activity against multidrug-resistantMycobacterium tuberculosis (Mtb) strains (Sun & Zhang, 1999) and inhibited its growth in infected human macrophages in a bacteriostatic manner (Fan et al., 2019). The same study also showed that it inhibited HIV replication in human macrophages via transcriptional effects.