Vanilla modulates the activity of antibiotics and inhibits efflux pumps in drug-resistant Pseudomonas aeruginosa

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ORIGINAL ARTICLE

Vanilla modulates the activity of antibiotics and inhibits efflux pumps in drug-resistant Pseudomonas aeruginosa Sagar S. Arya 1,2

&

Mansi M. Sharma 3

&

James E. Rookes 2

&

David M. Cahill 2

&

Sangram K. Lenka 1

Received: 26 May 2020 / Accepted: 2 October 2020 # Institute of Molecular Biology, Slovak Academy of Sciences 2020

Abstract Vanilla, a popular flavour extracted from Vanilla planifolia pods was tested for its antibiotic modulatory activity against extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates. Cured vanilla pod extract (VPE) was found nonbactericidal even at high doses (> 2000 µg/mL), however, it modulated the activity of several antibiotics at a sub-inhibitory concentration of 500 µg/mL. This modulation activity of VPE was observed for last line antibiotic options such as meropenem and tigecycline, as well as commonly used antibiotics like ciprofloxacin, levofloxacin and chloramphenicol. Further, it was observed that VPE inhibited the activity of efflux pumps in XDR P. aeruginosa clinical isolates. GC-MS spectral analysis revealed the dominance of vanillin, furfuran and some short-chain fatty acids in VPE. Therefore, further studies on the constituent ingredients in VPE are recommended to identify the active compounds and use them as antibiotic modulators and efflux pump inhibitors. Keywords Vanilla pod extract . Extensively drug-resistant . Pseudomonas aeruginosa . Antibiotic modulatory activity . GC-MS . Efflux pumps

Abbreviations VPE Vanilla pod extract PA Pseudomonas aeruginosa MDR Multidrug-resistant XDR Extensively drug-resistant EtBr Ethidium bromide ESβLs Extended spectrum β-lactamases MBLs Metallo-β-lactamases KPCs Klebsiella pneumoniae Carbapenemases MIC Minimum inhibitory concentration

Supplementary Information The online version of this article (https:// doi.org/10.2478/s11756-020-00617-5) contains supplementary material, which is available to authorized users. * Sangram K. Lenka [email protected] 1

TERI-Deakin Nanobiotechnology Centre, The Energy and Resources Institute, Gurugram, Haryana 122001, India

2

School of Life and Environmental Sciences, Deakin University, Waurn Ponds Campus, Victoria Geelong 3216, Australia

3

Center for Innovation Research and Consultancy, Pune 411018, India

Introduction Recent outbreaks of microorganisms that exhibit antibiotic resistance have occurred across the globe, indicating that we are on the cusp of a ‘post-antibiotic era’ (Jones et al. 2017). Sir Alexander Fleming anticipated this even before the widespread use of antibiotics and cautioned that the inappropriate use of penicillin could lead to the emergence of resistant ‘mutant forms’ (Levy 2002). As per his forecast, indiscriminate use of antibiotics has resulted in the development of drugresistant bacteria. One such ‘superbug’ is the gram-negative bacterium Pseudomonas aeruginosa which is now categorized as a critical threat to human health by Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) (Breidens