Ginger (Zingiber officinale) phytochemicals\u2014gingerenone-A and shogaol inhibit SaHPPK: molecular docking, molecular dynamics simulations and in vitro approaches

Shailima Rampogu,Rohit S Bavi,Ayoung Baek,Rajesh Goud Gajula,Yong Jung Kwon,Keun Woo Lee,Amir Zeb,Raj Kumar,Yongseong Kim

doi:10.1186/s12941-018-0266-9

Abstract

BackgroundAntibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Among several antibiotic resistant microbial consortium, Staphylococcus aureus is one of the most havoc microorganisms. Staphylococcus aureus encodes a unique enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), against which, none of existing antibiotics have been reported.MethodsComputational approaches have been instrumental in designing and discovering new drugs for several diseases. The present study highlights the impact of ginger phytochemicals on Staphylococcus aureus SaHPPK. Herein, we have retrieved eight ginger phytochemicals from published literature and investigated their inhibitory interactions with SaHPPK. To authenticate our work, the investigation proceeds considering the known antibiotics alongside the phytochemicals. Molecular docking was performed employing GOLD and CDOCKER. The compounds with the highest dock score from both the docking programmes were tested for their inhibitory capability in vitro. The binding conformations that were seated within the binding pocket showing strong interactions with the active sites residues rendered by highest dock score were forwarded towards the molecular dynamic (MD) simulation analysis.ResultsBased on molecular dock scores, molecular interaction with catalytic active residues and MD simulations studies, two ginger phytochemicals, gingerenone-A and shogaol have been proposed as candidate inhibitors against Staphylococcus aureus. They have demonstrated higher dock scores than the known antibiotics and have represented interactions with the key residues within the active site. Furthermore, these compounds have rendered considerable inhibitory activity when tested in vitro. Additionally, their superiority was corroborated by stable MD results conducted for 100 ns employing GROMACS package.ConclusionsFinally, we suggest that gingerenone-A and shogaol may either be potential SaHPPK inhibitors or can be used as fundamental platforms for novel SaHPPK inhibitor development.

Highlights

Antibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions
It is transmitted to foods via air, dust, and the lids covering the food containers [5, 6] and the food handlers carry the bacteria on their heads and noses, has an ability to colonize on the normal humans and transmit through direct contact with the bacteria-colonized person
Selection of the protein and its preparation SaHPPK structure used for current investigation, has been obtained from RCSB Protein Data Bank (PDB) with PDB code 3QBC [26], which is in complex with 2-amino-8-sulfanyl-1,9-dihydro-6H-purin-6-one (8MG)

Summary

Introduction

Antibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Staphylococcus aureus is a gram positive, non-motile bacterium This facultative anaerobe is a gram positive, non-motile bacterium hailing from Staphylococcaceae family, powered to infect every known mammalian species causing food poisoning [2, 3]. This is an ectopic commensal and is niched on mucosal membranes and skin of humans [4]. The horizontally acquired resistance may occur by alteration and inactivation of enzymatic drug, change in the drug binding site, dislocating the drug from its appropriate position and by drug efflux [21]. The effective treatment is hampered and promotes the infection and enhances the economic burden [23, 24]

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Results

Conclusion