Quorum Sensing Inhibition Attenuates the Virulence of the Plant Pathogen Ralstonia solanacearum Species Complex

Abstract

Strains of Ralstonia solanacearum species complex (RSSC) cause “bacterial wilt” on a wide range of plant species and thus lead to marked economic losses in agriculture. Quorum sensing (QS), a bacterial cell–cell communication mechanism, controls the virulence of RSSC strains by regulating the production of extracellular polysaccharide (EPS) and secondary metabolites, biofilm formation, and cellular motility. R. solanacearum strain OE1-1 employs (R)-methyl 3-hydroxymyristate (3-OH MAME) as a QS signal, which is synthesized by the PhcB methyltransferase and sensed by the PhcS/PhcRQ two-component system. We describe the design, synthesis, and biological evaluation of inhibitors of the phc QS system. Initial screening of a small set of QS signal analogues revealed that methyl 3-hydroxy-8-phenyloctanoate, named, PQI-1 (p hc quorum sensing inhibitor-1), inhibited biofilm formation by strain OE1-1. To improve its inhibitory activity, the derivatives of PQI-1 were synthesized, and their QS inhibition activities were evaluated. PQIs-2–5 evolved from PQI-1 more strongly inhibited not only biofilm formation but also the production of ralfuranone and EPS. Furthermore, RNA-Seq analysis revealed that the PQIs effectively inhibited QS-dependent gene expression and repression in strain OE1-1. On the other hand, the PQIs did not affect the canonical QS systems of the representative reporter bacteria. These antagonists, especially PQI-5, reduced wilting symptoms of the tomato plants infected with strain OE1-1. Taken together, we suggest that targeting the phc QS system has potential for the development of chemicals that protect agricultural crops from bacterial wilt disease.

Enhancing the Inhibition Potential of AHL Acylase PF2571 against Food Spoilage by Remodeling Its Substrate Scope via a Computationally Driven Protein Design

“…The main components of bacterial extracellular polymeric substances include EPSs, various proteins, and nucleic acids. As the main component of the biofilm skeleton, sufficient secretion of QS-mediated extracellular polymeric substances during the initial stages of bacterial adhesion is essential for biofilm formation . In this study, the production of EPS by A.…”

“…As the main component of the biofilm skeleton, sufficient secretion of QS-mediated extracellular polymeric substances during the initial stages of bacterial adhesion is essential for biofilm formation. 41 In this study, the production of EPS by A. veronii BY-8 was significantly inhibited by the tested enzymes, with the highest inhibitory rate of 54.65% observed for PF2571 H194Y, L221R (Figure 5E). Raman microscopy analysis was also used to detect the chemical constituents of the extracellular polymeric substances from A. veronii BY-8.…”

Quorum sensing-dependent invasion ofRalstonia solanacearumintoFusarium oxysporumchlamydospores

“…We plan to examine the effects of QS inhibitors (such as PQIs) (30) on this endoparasitism in detail.…”

“…As expected, this bacterium harbors two chitinase genes (RSp0275 and RSp0924), three glucanase genes (cbh-A, egl, and RSc0818), and two lipase (or esterase) genes (RSp0138 and RSp0161) (29). The previous RNA-Seq comparison between OE1-1 and ∆phcB showed that the expression of these genes is under the control of the phc QS system (30)(31)(32). We thus constructed these gene-deletion mutants and evaluated their invasion ability into F. oxysporum chlamydospores.…”

Silicon Controls Bacterial Wilt Disease in Tomato Plants and Inhibits the Virulence-Related Gene Expression of Ralstonia solanacearum

“…PhcA is activated by quorum sensing (QS), and it can induce the expression of xpsR and influence the biosynthesis of EPS [24]. Some chemical compounds, such as volatile organic compounds and R-methyl 3-hydroxymyristate, can inhibit biofilm formation, EPS production, and R. solanacearum colonization in plant roots [25,26]. Tahir et al (2017) found that Bacillus volatiles could reduce bacterial wilt incidence by changing the expression of the virulence factors (PhcA, T3SS, ESP, and chemotaxis) [27].…”