Exemplifying the next generation of antibiotic susceptibility intensifiers of phytochemicals by LasR-mediated quorum sensing inhibition

Abstract

There persists a constant threat from multidrug resistance being acquired by all human pathogens that challenges the well-being of humans. This phenomenon is predominantly led by Pseudomonas aeruginosa which is already resistant to the current generations of antibiotic by altering its metabolic pathways to survive. Specifically for this microbe the phenomenon of quorum sensing (QS) plays a crucial role in acquiring virulence and pathogenicity. QS is simply the cross talk between the bacterial community driven by signals that bind to receptors, enabling the entire bacterial microcosm to function as a single unit which has led to control P. aeruginosa cumbersome even in presence of antibiotics. Inhibition of QS can, therefore, be of a significant importance to curb such virulent and pathogenic strains of P. aeruginosa. Natural compounds are well known for their antimicrobial properties, of which, information on their mode of action is scarce. There can be many antimicrobial phytochemicals that act by hindering QS-pathways. The rationale of the current study is to identify such natural compounds that can inhibit QS in P. aeruginosa driven by LasR, PhzR, and RhlR dependent pathways. To achieve this rationale, in silico studies were first performed to identify such natural compounds which were then validated by in vitro experiments. Gingerol and Curcumin were identified as QS-antagonists (QSA) which could further suppress the production of biofilm, EPS, pyocyanin, and rhamnolipid along with improving the susceptibility to antibiotics.

Evidence for Complex Interplay between Quorum Sensing and Antibiotic Resistance in Pseudomonas aeruginosa

“…The effect of QS signal disruption in P. aeruginosa was previously shown to be synergistic with some antibiotics, namely, ciprofloxacin ( 38 – 40 , 44 ), ceftazidime ( 44 ), and gentamicin ( 38 ). However, it remains unclear if this approach can be synergistic with all antibiotic therapies.…”

A Comprehensive in vitro and in silico Assessment on Inhibition of CYP51B and Ergosterol Biosynthesis by Eugenol in Rhizopus oryzae

“…MD simulations are performed to determine if the assurance provided by the docking assessment for a ligand–protein interaction will really translate into practical terms [ 41 , 42 ]. Such MD simulation study can well establish the interaction of ligands with protein receptors with great degree of fidelity and scientific fraternity with increasing computational power make use of it to validate the hypothesis [ 43 – 45 ]. The current manuscript demonstrates the interaction of eugenol with CYP51B for making use of MD simulations which by far, to the best of our knowledge is not done making this the first report to assess the efficacy of eugenol to interact with CYP51B, where the interaction is found to be promising and at par with reference azole drug, clotrimazole.…”

Molecular insights on ar-turmerone as a structural, functional and pharmacophoric analogue of synthetic mosquito repellent DEET by comprehensive computational assessment

“…Lastly, the interaction of DEET and ar-turmerone with OBP1 was simulated at psychological conditions using MD simulations. Such MD simulation study can well establish the interaction of ligands with protein receptors with great degree of fidelity and scientific fraternity with increasing computational power make use of it to validate the hypothesis 39 – 46 . Findings of MD simulation consolidated the predictions of docking that ar-turmerone interacts with OBP1 at par with DEET.…”