Transcriptomic Analysis of Pseudomonas aeruginosa Response to Pine Honey via RNA Sequencing Indicates Multiple Mechanisms of Antibacterial Activity.

Ioannis Kafantaris,Ioannis Iliopoulos,Eleni Tsavea,Marios Nikolaidis,Grigoris D Amoutzias,Tilemachos G Dimitriou,Dimitris Mossialos,Christina Tsadila

doi:10.3390/foods10050936

Ioannis Kafantaris, Ioannis Iliopoulos + Show 6 more

Open Access

https://doi.org/10.3390/foods10050936

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Abstract

Pine honey is a unique type of honeydew honey produced exclusively in Eastern Mediterranean countries like Greece and Turkey. Although the antioxidant and anti-inflammatory properties of pine honey are well documented, few studies have investigated so far its antibacterial activity. This study investigates the antibacterial effects of pine honey against P. aeruginosa PA14 at the molecular level using a global transcriptome approach via RNA-sequencing. Pine honey treatment was applied at sub-inhibitory concentration and short exposure time (0.5× of minimum inhibitory concentration –MIC- for 45 min). Pine honey induced the differential expression (>two-fold change and p ≤ 0.05) of 463 genes, with 274 of them being down-regulated and 189 being up-regulated. Gene ontology (GO) analysis revealed that pine honey affected a wide range of biological processes (BP). The most affected down-regulated BP GO terms were oxidation-reduction process, transmembrane transport, proteolysis, signal transduction, biosynthetic process, phenazine biosynthetic process, bacterial chemotaxis, and antibiotic biosynthetic process. The up-regulated BP terms, affected by pine honey treatment, were those related to the regulation of DNA-templated transcription, siderophore transport, and phosphorylation. Pathway analysis revealed that pine honey treatment significantly affected two-component regulatory systems, ABC transporter systems, quorum sensing, bacterial chemotaxis, biofilm formation and SOS response. These data collectively indicate that multiple mechanisms of action are implicated in antibacterial activity exerted by pine honey against P. aeruginosa.

Highlights

Pseudomonas aeruginosa is a ubiquitous, Gram-negative opportunistic human pathogen that can cause acute and chronic human infections in hospitalized or immune-compromised patients [1,2]
The results clearly demonstrate that pine honey and manuka exert high anti-bacterial activity since both inhibited P. aeruginosa at 9% (v/v)
RNA sequencing (RNA-seq) analysis revealed that pine honey significantly affected the trascriptomic profile of P. aeruginosa by increasing significantly the expression of 189 genes and by reducing significantly the expression of 274 genes

Summary

Introduction

Pseudomonas aeruginosa is a ubiquitous, Gram-negative opportunistic human pathogen that can cause acute and chronic human infections in hospitalized or immune-compromised patients [1,2]. It infects the airway, urinary tract, burns, wounds, surgical site infections and causes systemic blood infections that can lead to death [3]. P. aeruginosa can adapt to a wide variety of environmental conditions and exhibits a remarkable high multidrug resistance by the formation of biofilms [6,7,8]. Considering its high prevalence associated with high mortality rates and lack of treatment options, this pathogen has been identified by the World Health Organization as a critical research priority for the development of alternative drugs and novel therapeutic strategies [9]

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