Potential of 1-(1-napthylmethyl)-piperazine, an efflux pump inhibitor against cadmium-induced multidrug resistance in Salmonella enterica serovar Typhi as an adjunct to antibiotics

Heavy metal-induced selection and proliferation of antibiotic resistance: A review

“…, and Cr 2 O 7 − (Harrison et al, 2009;Kaur et al, 2021). Cd and Cu 2+ ions also act as an inducer to derepress the multiple antibiotic resistance regulatory operon marRAB in both Salmonella sp.…”

“…Besides these co-selection strategies, combined resistance to antibiotics and metals is aided by the formation of biofilms also. The heavy metal or antibiotic stress induces the production of certain substances that aid Kaur et al (2021) in cellular adhesion along with the production of extracellular polymeric substances (EPS) in planktonic cells which subsequently helps in the formation of biofilms (Baker-Austin et al, 2006). Induction of biofilm due to production of EPS as a survival strategy on exposure to metals has been reported by García-Meza et al (2005) and Kidambi et al (1995) in Phormidium (cyanobacteria) and Pseudomonas species respectively.…”

“…Cu or Zn along with the BaeR response regulator induces expression of acrD and mdtABC genes which code for AcrD and MdtABC multidrug efflux pumps, responsible for antibiotic resistance in Salmonella enterica serovar Typhimurium (Nishino et al, 2007). Similarly, the expression of SoxS, which is a universal response regulator protein that regulates multidrug efflux pump AcrAB in E. coli and Salmonella sp., is upregulated in response to oxidative stress caused by ions, such as Cd, Cu 2+ , and Cr 2 O 7 − (Harrison et al, 2009; Kaur et al, 2021). Cd and Cu 2+ ions also act as an inducer to derepress the multiple antibiotic resistance regulatory operon marRAB in both Salmonella sp.…”

“…Pathogenicity of the micro‐organism is also reduced by these agents as they have been reported to inhibit biofilm formation (Sabatini et al, 2017; Anes et al, 2019; Ferrer‐Espada et al, 2019). Use of 1‐(1‐napthylmethyl)‐piperazine or NMP, one such active efflux pump inhibitor, was reported to reverse AcrAB efflux pump mediated MDR in cadmium adapted Salmonella Typhi cells (Kaur et al, 2021). Therefore, discovering more such inhibitor molecules, which on administration with antibiotics can reverse MDR in micro‐organisms, can be very beneficial for the medical community.…”

Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics

“…As for Gram-positive specific antibiotics whose activity is potentiated by OM-disrupting synergists, we have chosen to focus on clinically used agents that are most commonly evaluated for synergy with OM disrupters: erythromycin, rifampicin, vancomycin, and novobiocin. , This criterion has, for example, led to the exclusion of OM-disrupting agents for which synergy was reported with macrolide antibiotics other than erythromycin. − Also, while the specific media conditions used in antibacterial assays can strongly influence the outcome of synergy studies, for the sake of brevity, we do not include this level of detail here and instead provide clear referencing of the original studies wherein such information can be found. In addition, to further streamline the Review, synergists for which an OM-disrupting mechanism was not clearly demonstrated are not here discussed in detail. − Furthermore, synergists that specifically engage with Gram-negative targets and subsequently cause OM disruption as a secondary effect are not discussed in this Review. − …”