Synergistic effects of nanoemulsion and deferiprone (1,2 dimethyl-3-hydroxypyrid-4-one) on multi-drug resistant acinetobacter baumannii

Abstract

Nosocomial infections caused by Acinetobacter baumannii (A. baumannii) are exceedingly difficult to treat, particularly in immune-compromised patients. Nanoemulsions (NEs) are a distinctive category of disinfectants that have wide range of bactericidal, fungicidal and antiviral properties by damaging their outer membranes. The inhibiting potential of iron chelators such as deferiprone (DF) used as remedial agent for different microbial groups. Combining new generation disinfectant NEs and the iron chelator DF is a logical approach to control of A. baumannii planktonic and biofilm infections. Present studies investigated the bactericidal efficacy of NE with DF by testing their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against four strains of A. baumannii. We analyzed adherence of the planktonic form both with and without deferiprone to determine possible enhancement effects. The mechanism of nanoemulsion with deferiprone (NE/DF) was quantified by LIVE/DEAD staining biofilm assay and scanning electron microscopy. DF does not affect the stability of the nanoemulsion and the combined forms show high stability. From MBC, NE/DF showed enhanced activity up to 2-to 3.3-fold compared to nanoemulsion and deferiprone alone. Combined nanoemulsion with deferiprone showed higher adherence inhibition compared to the individual forms. From confocal imaging, the level of dead cell intensity was 84.9% to 96.6% in NE/DF treated groups. Bacteria treated with NE, DF and NE/DF confrms morphological variations when compared to pili-bonded integrated control cells. We propose that biofilm destruction starts from pili removal followed by membrane destruction. These results leave a concrete evidence for the employment of nanoemulsion with deferiprone for the treatment of against drug resistant A. baumannii.