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.