Products Cited in Publications Worldwide Computational and experimental strategies for combating MBL P. aeruginosa (MBLPA) biofilms using phytochemicals: Targeting the quorum sensing network

Computational and experimental strategies for combating MBL P. aeruginosa (MBLPA) biofilms using phytochemicals: Targeting the quorum sensing network

Maryum Fakhar; Mehboob Ahmed; Anjum Nasim Sabri

DOI:

Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, ubiquitously found in nature and causative agent in many infections. Due to increased antibiotic resistance, there is a need to develop more robust agents from natural sources. In this study, we worked on two metallo-β-lactamase (MBL) producing Pseudomonas aeruginosa strains and targeted the mechanism (QS) of these bacteria to combat antibiotic resistance. Our study aimed at using phytochemicals which have been used since centuries in herbal medicine. We used fifteen commercially available phytochemicals and check their effects on biofilm formation, and inter-related mechanisms. Sub-inhibitory concentration of isoliquiritin inhibited biofilm formation 55 % in P8 at day 6 and 48 % in P6 at day 6; 83 % in P6 and 61 % in P8 whereas sub-inhibitory concentration of suppressed biofilm formation by 48 % in P8 at day 6 and 44 % in P6 at day 6; 69 % in P6 and 48 % in P8, respectively. The results indicated isoliquiritin, , , and to be the potential candidates in inhibiting QS and related mechanisms. Isoliquiritin which was never been used before against biofilm and QS related studies, showed remarkable results and found to be more efficient in inhibiting QS than –a known QS inhibitor. For examining the molecular interaction between phytochemicals and QS, In-silico molecular docking was performed between phytoligands and four QS proteins (Las I, Las R, RhlI and Rhl R). In-silico docking analysis revealed that isoliquiritin showed strong bond with amino acids (Trp34, Asp35, Asp35, Tyr105, Arg104, Val138, Thr140) present at the active site of RhlI with binding energy value of −8.4 kcal/mol as compared to that of with Rhl1 (−7.3 kcal/mol). In conclusion, our study may help in controlling nosocomial infections caused by carbapenem-resistant metallo beta-lactamase P. aeruginosa (MBL-PA) by utilizing these phytochemicals in biofilms disruption and inhibition. Moreover their synergism with antibiotics may help in lowering the MIC of carbapenem antibiotics against such Multi-drug resistant strains.

Keywords

; Biofilm ; MBL Pseudomonas ; Isoliquiritin

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