Antibiofilm potential of isolated diterpenes from polyalthia longifolia and its derivatives against methicillin-resistant Staphylococcus aureus

Abstract

Background:The emerging antimicrobial resistance will be responsible for more casualty by 2050 (AMR review, UK). In this context, a group of antimicrobial resistant ESKAPE pathogen is of prime importance. Methicillin-resistant Staphylococcus aureus is one of the members of ESKAPE pathogens, is clinically important and responsible for various major life-threatening nosocomial infections. Its inherent antibiotic resistance and biofilm-forming capability make it more persistent and difficult to encounter. This scenario will demand to search for new molecules with better antimicrobial and anti-virulence properties against MRSA. Polyalthia longifolia is an ornamental plant containing clerodane diterpenoids (i.e. 16-oxo-cleroda-3, 13( 14) E-diene-15 oic acid (1) and kolavenic acid (2) which posses important pharmacological properties was isolated from leaves of this plant further derivatized to synthetic lactones and studied for their antibacterial and biofilm inhibitory potential.Methods and materials: Compound 1 (16-oxo-cleroda-3, 13(14) E-diene-15 oic acid) and Compound 2 (Kolavanic acid) were isolated from the leaves of Polyalthia longifolia; Compound 1 was further derivatized to synthetic lactones as compound 3, 4, 5 and 6. The isolated compounds and synthetic lactones were screened for their antimicrobial and biofilm inhibition and eradication was evaluated by crystal violet based assay, MTT and calculating CFU/ml. Fluorescence and electron microscopy was conducted to confirm the biofilm inhibitory activities. Molecular mechanism of biofilm inhibition was done by evaluating gene expression analysis by using PCR.Results: Among the tested compounds 1 and 3 were found to have better antistaphylococcal properties with better biofilm inhibiting potential. At 10-30 g/ml 1 and 3 were found to be antivirulence, antibacterial and antibiofilm. Compound 1 was also found to have better biofilm eradicating potential as compared to compound 3. Biofilm inhibitory potential of both the compounds was further confirmed by fluorescence and scanning electron microscopy at MIC and sub MIC levels. Parent compound (1) and its synthetic ␥-lactone (3) significantly delayed the bacterial growth after their short exposure of 10 min. These compounds also altered the gene expression of MRSA biofilm-related genes (icaA). Conclusion:The observed anti-virulence properties and delayed bacterial growth suggested these compounds can be a drug lead to overcome MRSA related infections.

New Insights into the Antimicrobial Potential of Polyalthia longifolia—Antibiofilm Activity and Synergistic Effect in Combination with Penicillin against Staphylococcus aureus

“…Therefore, we consider PlLm and PlLe antibacterial activity very attractive, suggesting the potential of developing new drugs to overcome MRSA-related infections. Our conclusion is supported by a comparative literature survey that revealed the same potential of P. longifolia extracts against clinical isolates of MRSA [ 11 , 29 , 31 ]. The important antibacterial activity of P. longifolia leaf extracts could also be explained in relation to its chemical composition.…”

“…Both PlLm and PlLe extracts were active against a MRSA clinical isolate, with MIC values of 0.312 and 0.624 mg/mL, respectively. Methicillin-resistant Staphylococcus aureus is an ESKAPE pathogen, with high clinical importance and which is responsible for various major life-threatening nosocomial infections [ 29 ]. Most ESKAPE pathogens are multidrug-resistant strains, which is one of the greatest challenges in clinical practice [ 30 ].…”