title: Adjuvant effect of cranberry proanthocyanidin active fraction on antivirulent property of ciprofloxacin against Pseudomonas aeruginosa.
abstract: Quorum sensing inhibitors (QSIs) act as antivirulent agents since quorum sensing (QS) plays a vital role in regulating pathogenesis of Pseudomonas aeruginosa. However, application of single QSI may not be effective as pathogen is vulnerable to successful mutations. In such conditions, combination of QSIs can be exploited as there can be synergistic or adjuvant action. In the present study, we evaluated the antivirulence efficacy of combination of Vaccinium macrocarpon proanthocyanidin active fraction (PAF) and ciprofloxacin (CIP) at their sub-MICs using standard methods followed by analysis of their mode of action on QS using TLC and molecular docking. There was significant improvement in action of CIP when it was combined with PAF in reducing the QS controlled virulence factors (p < 0.05), motilities and biofilm of P. aeruginosa. TLC profiles of QS signals [(Acyl homoserine lactone (AHL) and Pseudomonas quinolone signal (PQS)] indicated that CIP in combination with PAF, besides showing inhibitory action on production of AHLs, also modulated production and inactivation of PQS. Docking scores also supported the observation. We therefore hypothesize that PAF-CIP combination, having improved anti-virulence property; can be exploited as a potent drug pairing against P. aeruginosa.
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh, India.
authors.forename: Anitha
authors.initials: A
authors.lastname: Vadekeetil
authors.affiliation: Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chennai, India.
authors.forename: V
authors.initials: V
authors.lastname: Alexandar
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chhibber
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh, India. Electronic address: kusum_harjai@hotmail.com.
authors.forename: Kusum
authors.initials: K
authors.lastname: Harjai
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000378:metabolism; D054742:Acyl-Butyrolactones / Q000494:pharmacology; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology*; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D015363:Quinolones / Q000378:metabolism; D053038:Quorum Sensing / Q000187:drug effects; D029799:Vaccinium macrocarpon / Q000737:chemistry*; D014774:Virulence / Q000187:drug effects
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; D054742:Acyl-Butyrolactones; D000277:Adjuvants, Pharmaceutic; D000900:Anti-Bacterial Agents; D010936:Plant Extracts; D044945:Proanthocyanidins; D015363:Quinolones; C088386:homoserine lactone; C013221:proanthocyanidin; D002939:Ciprofloxacin; D015107:4-Butyrolactone
keywords: Antivirulent agents; Ciprofloxacin; Proanthocyanidin active fraction; Pseudomonas aeruginosa; Quorum sensing inhibitors