Background:
Antibiotic-resistant members of the family Enterobacteriaceae are among the
serious threats to human health globally. This study reports 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 anti-pathogenic activity of PGPE against the
gram-negative 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 transcriptome approach.
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 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 expression of a total of 66 genes in S. marcescens by ≥1.5 fold.
Conclusion:
PGPE’s anti-virulence effect 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.