CpxR negatively regulates the production of xenocoumacin 1, a dihydroisocoumarin derivative produced by Xenorhabdus nematophila

Abstract

Xenocoumacin 1 (Xcn1), a major antimicrobial compound produced by Xenorhabdus nematophila, has great potential for use in agricultural productions. In this study, we evaluated the effects of CpxR, a global response regulator associated with the mutualism and pathogenesis of X. nematophila, on the antimicrobial activity and Xcn1 production. The mutation of cpxR could promote the production of Xcn1 significantly with its level in ΔcpxR mutant being 3.07 times higher than that in the wild type. Additionally, the expression levels of xcnA-L genes, which are responsible for the production of Xcn1, were increased in ΔcpxR mutant while the expression levels of xcnMN, which are required for the conversion of Xcn1 into Xcn2 was reduced. Noticeably, Xcn2 was also enhanced on account of the conversion of excessive Xcn1 in spite of low expression levels of xcnM and xcnN in ΔcpxR mutant. The transcriptional levels of ompR and lrp, encoding the global response regulators OmpR and Lrp which negatively and positively regulate the production of Xcn1 were concurrently decreased and increased, respectively. Correspondingly, ΔcpxR mutant also exhibited increased antimicrobial activities in vitro and in vivo. Together, these findings suggest that CpxR negatively regulates xcnA-L genes expression while positively regulating xcnMN expression in X. nematophila YL001, which led to a high yield of Xcn1 in ΔcpxR mutant.

Nematophin, an Antimicrobial Dipeptide Compound From Xenorhabdus nematophila YL001 as a Potent Biopesticide for Rhizoctonia solani Control

“…X. nematophila YL001 is a valuable producer of natural compounds with pesticidal properties. Its fermentation broth was indicated to possess strong antimicrobial activity against some plant pathogens in vitro and in vivo , including P. infestans and B. cinerea (Guo et al, 2017; Zhang et al, 2018). Additionally, several pesticidal compounds have been identified from other X. nematophila stains, such as xenocoumacins (McInerney et al, 1991; Yang et al, 2011; Zhou et al, 2016), nematophin (Li et al, 1997a,b), PAX (peptide-antimicrobial- Xenorhabdus ) peptides (Gualtieri et al, 2009; Fuchs et al, 2011), benzylideneacetone (Ji et al, 2004), xenortides, and xenematides (Lang et al, 2008).…”

“…The antimicrobial activity of three isolated compounds against the mycelial growth of 10 plant pathogens was performed as described in previous research with slight modifications (Zhang et al, 2018). Briefly, the three compounds were dissolved in dimethyl sulfoxide (DMSO) to prepare their respective stock solutions with a concentration of 10,000 μg/ml.…”

“…Previous studies revealed that the cell-free culture of X. nematophila YL001 exhibited potent antimicrobial activity against some plant pathogens in vitro and in vivo , including P. infestans and B. cinerea (Guo et al, 2017; Zhang et al, 2018). However, no purified bioactive compounds were obtained from this bacterial strain, although many metabolites of novel structures and strong antimicrobial activity were purified and identified from strains of genus Xenorhabdus (Dreyer et al, 2018) including odilorhabdins (Pantel et al, 2018), cabanillasin (Houard et al, 2013), and bicornutin-A (Böszörményi et al, 2009).…”

Antimicrobial Activity and Identification of the Biosynthetic Gene Cluster of X-14952B From Streptomyces sp. 135

“…The inhibitory effects of metabolites on the mycelial growth of pathogenic fungi and oomycetes were determined by the inhibition mycelial growth rate method as described by Zhang et al (2019) with a few alterations. Cell-free fermentation broth (5 mL) was mixed well with molten PDA medium (45 mL) at approximately 40 to 50°C and poured evenly into three 90-mm diameter Petri dishes.…”

“…For determination of the antifungal activity of the isolated compound, the mycelial growth rate method was utilized ( Zhang et al, 2019 ). The compound was dissolved in methanol and a stock solution of 20 mg/mL was prepared.…”