Molecular Interaction Studies for Inhibition of the Streptococcus pneumoniae Competence Stimulating Peptide (CSP1) by Potent Plant-Derived Compounds.

Pharmaceutical Science-Bioinformatics for Better Health Care

Abstract

Antimicrobial resistance (AMR) is an immense medical concern; it is among the top causes of fatality worldwide. The development  of  resistance  occurs  most  frequently  with  nosocomial  and  community-acquired  infections,  among  which Streptococcus  pneumoniae is  a  common  causative  organism.  This  study  is  focused  on  inhibiting  the  quorum-sensing  (QS) mechanism using plant compounds as an alternate strategy to avert AMR. A major factor in the development of AMR is genetic variability. S. pneumoniae genetic variability is enabled by the natural competence and transformation of the organism, a trait historically most notable. It is regulated by the expression of com loci genes. The com loci regulation and the regulation of other subsequent  signaling  pathways  are  a  QS  mediated  system,  for  which  the  competence  stimulating  peptide  (CSP1)  is  the autoinducer. CSP1 was selected as the target for inhibition studies due to its significant role in driving bacterial communication via QS, leading to competence, virulence, and resistance. Plant-derived compounds present a vast scope for developing antimicrobials; in this study, we have proposed using the plant compounds to avert the development of AMR by inhibiting the factor directly responsible, i.e. CSP1. Five natural plant compounds, selected based on the ADMET profile, were studied for inhibition of CSP1; these compounds were curcumin, ellagic acid, eugenol, kaempferol, tinosporinone. These five compounds had credible drug likeliness with no acute toxicity and satisfactory bioavailability score. The molecular docking studies between CSP1 and the selected five compounds revealed a satisfactory interaction with the binding pocket of CSP1 and act as potential inhibitors.