Background: Antibiotic-resistant members of the family Enterobacteriaceae are
among the serious threats to human health globally. This study reports the anti-pathogenic activity
of Punica granatum peel extract (PGPE) against a multi-drug resistant, beta-lactamase producing
member of this family i.e. Serratia marcescens.
Objective: This study aimed at assessing the anti-pathogenic activity of PGPE against the gramnegative
bacterial pathogen S. marcescens and identifying the molecular targets of this extract in
the test bacterium.
Methods: Effect of PGPE on S. marcescens growth and quorum sensing (QS)-regulated pigment
production was assessed through broth dilution assay. In vivo anti-infective and prophylactic activity
of PGPE was assessed employing the nematode worm Caenorhabditis elegans as a model
host. Differential gene expression in PGPE-exposed S. marcescens was studied through a whole
Results: PGPE was able to modulate QS-regulated pigment production in S. marcescens without
exerting any heavy growth-inhibitory effect at concentrations as low as ≥2.5 μg/mL. It could attenuate
the virulence of the test bacterium towards the worm host by 22-42% (p≤0.01) at even
lower concentrations (≥0.5 μg/mL). PGPE also exerted a post-extract effect on S. marcescens.
This extract was found to offer prophylactic benefit too, to the host worm, as PGPE-pre-fed
worms scored better (34-51%; p≤0.001) survival in face of subsequent bacterial attack. Differential
gene expression analysis revealed that PGPE affected the expression of a total of 66 genes in
S. marcescens by ≥1.5 fold.
Conclusion: The anti-virulence effect of PGPE against S. marcescens is multifaceted, affecting
stress-response machinery, efflux activity, iron homeostasis, and cellular energetics of this bacterium
notably. Among the major molecular targets identified in this study are LPS export
transporter permease (LptF), t-RNA pseudouridine synthase (TruB), etc.