Vanillin mediated green synthesis and application of gold nanoparticles for reversal of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates

Abstract

Antimicrobial resistance (AMR) is a serious concern in pathogenic bacteria. As a new approach to addressing AMR, we report here the green synthesis of vanillin capped gold nanoparticles (VAuNPs) using the popular flavouring molecule vanillin (C 8 H 8 O 3 ) as a reducing and capping agent. Physicochemical characterization revealed that the synthesised VAuNPs were stable and crystalline in nature. VAuNPs were non-bactericidal even at high concentration (>2000 μg/ml). The antibiotic potentiation activity was studied in combination with seven widely used antibiotics against extremely drug resistant (XDR) Pseudomonas aeruginosa . Major reductions in minimum inhibitory concentrations (MIC, 10–14-folds) of the antibiotics meropenem (10 fold) and trimethoprim (14 fold) were observed in the presence of VAuNPs (50 μg/ml). Furthermore, it was found that VAuNPs in combination with meropenem or trimethoprim provided 1.5–3-fold better potentiation effects than that of vanillin alone. Use of an ethidium bromide agar cart wheel assay indicated that VAuNPs can block the activity of efflux pumps. High reduction in the MIC of antibiotics was therefore attributed to the efflux pump repression activity of VAuNPs. Further, RT-qPCR of clinically relevant MexAB-OprM efflux pump components showed down-regulation in mexB and OprM transcripts in VAuNPs treated P. aeruginosa clinical isolates. Our results reveal that VAuNPs impart susceptibility to the last line antibiotics meropenem, trimethoprim and few widely used antibiotics in XDR P. aeruginosa clinical isolates that display resistance to these antibiotics. Therefore, this study indicate the ability of VAuNPs and vanillin to be used as antibiotic adjuvants for inhibiting bacterial efflux pumps to potentiate antibiotics for addressing AMR problem affecting human health and environment.

Tannic Acid-Stabilized Silver Nanoparticles Used in Biomedical Application as an Effective Antimelioidosis and Prolonged Efflux Pump Inhibitor against Melioidosis Causative Pathogen

“…The results showed no fluorescence emission of bacteria on 2 µg/mL EtBr agar. This result indicates that three different strains of B. pseudomallei before and after the 30th generation passage had efflux pump activity to pump EtBr (as an efflux pump substrate) out of the cells [ 26 ] ( Figure 7 b).…”

Vanillin: a review on the therapeutic prospects of a popular flavouring molecule

“…It was reported to regulate the activities of gentamycin, imipenem, norfloxacin and spectinomycin used against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli (Bezerra et al 2017;Brochado et al 2018). It also potentiated the activities of some commonly used and last line antibiotics like chloramphenicol, ciprofloxacin, levofloxacin, tigecycline, meropenem, trimethoprim and fosfomycin against extremely drug-resistant P. aeruginosa clinical isolates (Arya et al 2019(Arya et al , 2020. These studies suggest that vanillin has the potential to be used as an antibiotic adjuvant in future.…”

“…Vanillin is either isolated from vanilla extract or is chemically synthesized from guaiacol. Besides being known for flavour and fragrance, it has diverse bioactive properties, namely anticancer, neuroprotective, antibiotic potentiation, and anti-quorum sensing (Arya et al 2019;Bezerra et al 2016;Li et al 2018). Moreover, the bioactivities of curcumin are now attributed to the constituent and stable degradation products, i.e.…”

The Demand for New Antibiotics: Antimicrobial Peptides, Nanoparticles, and Combinatorial Therapies as Future Strategies in Antibacterial Agent Design

“…Finally, the use of more than one agent broadens the antibacterial spectrum of the empirical therapy and thus ensures that at least one agent will cover the infecting organism (Gurjar et al, 2014). such as gold (El-Sheekh and El Kassas, 2014;Kalita et al, 2016;Al-Mawlawi and Obaid, 2019;Arya et al, 2019;Nishanthi et al, 2019;Yang et al, 2019), copper (Khurana et al, 2016;Woźniak-Budych et al, 2017;Murugan, 2018;Selvaraj et al, 2019), and zinc (Banoee et al, 2010;Bhande et al, 2013) have been used in combination with a variety of antibiotic families to enhance bactericidal efficacy.…”

“…They can be used in combinatorial treatments with currently used antibiotics for enhanced antimicrobial activity ( Shahverdi et al, 2007 ; Kora and Rastogi, 2013 ; Naqvi et al, 2013 ; Singh et al, 2013 ; Panácek et al, 2016 ; Lopez-Carrizales et al, 2018 ; Perveen et al, 2018 ; Vazquez-Muñoz et al, 2019 ). Nonetheless, some other MNPs such as gold ( El-Sheekh and El Kassas, 2014 ; Kalita et al, 2016 ; Al-Mawlawi and Obaid, 2019 ; Arya et al, 2019 ; Lee and Lee, 2019 ; Nishanthi et al, 2019 ; Yang et al, 2019 ), copper ( Khurana et al, 2016 ; Woźniak-Budych et al, 2017 ; Murugan, 2018 ; Selvaraj et al, 2019 ), and zinc ( Banoee et al, 2010 ; Bhande et al, 2013 ) have been used in combination with a variety of antibiotic families to enhance bactericidal efficacy.…”