In vitro evaluation of the reason(s) of low level antimicrobial activity of some plant-based alkaloids (noscapine, caffeine and vincamine) on various strains of multidrug resistance Pesudomonas aeruginosa

Most plant compounds have very low level of antimicrobial activity than antibiotics especially against Gram-negative bacteria (MIC=100-1000µg/ml). Recently، scientists believe that the bacterial efflux pumps are responsible for this problem. These transmembrane proteins (efflux pumps) are capable of recognizing and expelling a variety of structually unrelated antimicrobial agents including plant compounds from the bacterial cell and subsequenly conferring resistance to these compounds. The aim of this study was to investigate the main reason (s) of low level antimicrobial activity of plant-based alkaloids; noscapine، caffein and vincamine، against representative highly resistant Gram negative bactria (Pseudomonas aeruginosa). Most alkaloids are the part of plant phytoalexins which their levels increase strongly in response to microbial invasion، this means that most alkaloids are plant antimicrobial agents but noscapine، caffein and vincamine did not actually show any antimicrobial activity in a direct susceptibility tests in vitro. Intrinsic antimicrobial activity (intraction between alkaloids and PAβN (inhibitor of Gram negative bacteria)) or efflux pump inhibitory properties (synergy between alkaloids and levofloxacin (substrate of the efflux pumps in (Pseudomonas aeruginosa) of noscapine، affeine and vincamine were assessed by a checkerboard titration assay. Results showed that caffeine and vincamine were intrinsically the plant antimicrobial compounds. With disrupting the function of MexAB-OprM in nalB highly resistant strain of Pseudomonas aeruginosa by PAβN، antimicrobial activities of caffeine and vincamine were increased by 17-and 8-fold، respectively. Therefore، it could be said that bacterial efflux pumps are a major factor in the weakening of antimicrobial activity of plant compounds. It appears that inhibition of these pumps may significantly improve the clinical performance of these natural compounds and thereby hoped that plant antimicrobials similar to systemic antibiotics will find its way to the field of clinical treatment in future.