3-Benzyl-Hexahydro-Pyrrolo[1,2-a]Pyrazine-1,4-Dione Extracted From Exiguobacterium indicum Showed Anti-biofilm Activity Against Pseudomonas aeruginosa by Attenuating Quorum Sensing.

Vijay K Singh,Avinash Mishra,Bhavanath Jha

doi:10.3389/fmicb.2019.01269

Vijay K Singh, Avinash Mishra + Show 1 more

Open Access

https://doi.org/10.3389/fmicb.2019.01269

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Abstract

Bacterial cell-to-cell communication promotes biofilm formation and can potentially lead to multidrug resistance development. Quorum sensing inhibition (QSI) is an effective and widely employed strategy against biofilm formation. The extract from Exiguobacterium indicum SJ16, a gram-positive bacterium, isolated from the rhizosphere of Cyperus laevigatus showed significant anti-quorum sensing activity (about 99%) against the reference Chromobacterium violaceum CV026 strain without exerting any antibacterial effect. The potentially active QSI compound identified in the SJ16 extract was 3-Benzyl-hexahydro-pyrrolo[1, 2-a]pyrazine-1,4-dione. The SJ16 extract containing this active compound showed significant anti-quorum sensing activity against a model quorum sensing bacterium strain Pseudomonas aeruginosa PAO1 and a clinical isolate P. aeruginosa PAH by preventing biofilm formation without attenuating the cell growth within the biofilm. More specifically, the SJ16 extract changed the topography and architecture of the biofilm, thus preventing bacterial adherence and further development of the biofilm. Furthermore, it decreased virulence factors (rhamnolipid and pyocyanin), the bacterial motility, as well as the elastase, and protease activities in P. aeruginosa. Microarray analysis revealed the differential expression of quorum sensing regulatory genes. Based on these results, we herein propose a hypothetical model, characterizing the role of this QSI agent in the transcriptional regulation of quorum sensing in P. aeruginosa PAO1, demonstrating that this compound has significant drug-development potential. Further research is required to delineate its possible applications in therapeutics in the context of biofilm forming bacterial infections.

Highlights

The diseases caused by pathogenic bacteria are controlled, prevented, and treated with a number of antibiotics which inhibit essential bacterial processes, such as cell wall synthesis, DNA replication, or protein biosynthesis
Out of 56 bacterial axenic cultures which were obtained from the rhizosphere of C. laevigatus L., two axenic cultures (SJ01 and SJ16) showed anti-Quorum sensing (QS) activity (Singh et al, 2017)
The whole-cell Fatty acid methyl ester (FAME) profile of the E. indicum SJ16 bacterium demonstrated an abundance of the iso-C17:0 (17.39%), iso-C15:0 (14.79%) and anteiso-C13:0 (11.36%) fatty acids (Supplementary Figure S2)

Summary

Introduction

The diseases caused by pathogenic bacteria are controlled, prevented, and treated with a number of antibiotics which inhibit essential bacterial processes, such as cell wall synthesis, DNA replication, or protein biosynthesis. Antibiotics have long become the commonplace in our effort to tackle infectious diseases (Chu et al, 2014). Quorum sensing (QS) is directly involved in pathogenesis of infectious disease, by regulating the biofilm formation, the production of multiple virulence factors, as well as the motility of bacteria (Singh et al, 2017). In QS system, molecular cascades regulate the gene expression and determine the fate of bacterial biofilms (Ganin et al, 2015). In this context, gram-negative bacteria communicate through small diffusible molecules, such as acyl homoserine lactones, whereas gram-positive bacteria use autoinducer peptides for their communication (Galloway et al, 2011)

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