Structure elucidation and biosynthesis of lysine-rich cyclic peptides in Xenorhabdus nematophila

Fuchs, Sebastian W.; Proschak, Anna; Jaskolla, Thorsten W.; Karas, Michael; Bode, Helge B.

doi:10.1039/c1ob05097d

Cited by 80 publications

(88 citation statements)

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“…Indeed, the number of NRPS/PKS modules, the functional units of the multimodular NRPS–PKS enzymes, was found to be significantly smaller in the Xp_G6 genome (21 modules, 106 kb) than in the Xb , Xd and Xn genomes (56–79 modules, 253–413 kb). Furthermore, the pax locus, encoding NRPS enzymes involved in the synthesis of PAX peptides, which are lysine-rich antifungal cyclolipopeptides (Gualtieri et al 2009; Fuchs et al 2011), and an undescribed NRPS locus, weakly similar to a Pseudomonas syringae locus, were specifically absent from the present Xp_G6 genome, but present in the other three Xenorhabdus genomes (table 5). This genomic pattern highlights the low potential of Xp_G6 for the synthesis of secondary metabolites.…”

Section: Resultsmentioning

confidence: 99%

“…This genomic pattern highlights the low potential of Xp_G6 for the synthesis of secondary metabolites. These metabolites have a wide range of bioactive properties and have been reported to be involved in antimicrobial activities, cytotoxic activity, and immunomodulation in entomopathogenic bacteria (Gualtieri et al 2009; Park et al 2009; Vallet-Gely et al 2010; Fuchs et al 2011; Stein et al 2012; Theodore et al 2012). Their absence from Xp_G6 may limit the capacity of this bacterium to kill the insect on its own.…”

Section: Resultsmentioning

confidence: 99%

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Attenuated Virulence and Genomic Reductive Evolution in the Entomopathogenic Bacterial Symbiont Species, Xenorhabdus poinarii

Ogier

Pagès

Bisch

et al. 2014

Genome Biology and Evolution

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Bacteria of the genus Xenorhabdus are symbionts of soil entomopathogenic nematodes of the genus Steinernema. This symbiotic association constitutes an insecticidal complex active against a wide range of insect pests. Unlike other Xenorhabdus species, Xenorhabdus poinarii is avirulent when injected into insects in the absence of its nematode host. We sequenced the genome of the X. poinarii strain G6 and the closely related but virulent X. doucetiae strain FRM16. G6 had a smaller genome (500–700 kb smaller) than virulent Xenorhabdus strains and lacked genes encoding potential virulence factors (hemolysins, type 5 secretion systems, enzymes involved in the synthesis of secondary metabolites, and toxin–antitoxin systems). The genomes of all the X. poinarii strains analyzed here had a similar small size. We did not observe the accumulation of pseudogenes, insertion sequences or decrease in coding density usually seen as a sign of genomic erosion driven by genetic drift in host-adapted bacteria. Instead, genome reduction of X. poinarii seems to have been mediated by the excision of genomic blocks from the flexible genome, as reported for the genomes of attenuated free pathogenic bacteria and some facultative mutualistic bacteria growing exclusively within hosts. This evolutionary pathway probably reflects the adaptation of X. poinarii to specific host.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Attenuated Virulence and Genomic Reductive Evolution in the Entomopathogenic Bacterial Symbiont Species, Xenorhabdus poinarii

Ogier

Pagès

Bisch

et al. 2014

Genome Biology and Evolution

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“…X. nematophila contains 7 NRPS and NRPS-PKS gene clusters (see Table S1 in the supplemental material). The NRPS gene clusters encoding xenocoumacin (11), PAX lysine-rich lipopeptide (29,30), rhabdopeptide (31), and xenortide (32) had been identified previously. We refer to the remaining three clusters that had not been previously studied as clusters A, C, and F.…”

Section: Resultsmentioning

confidence: 99%

“…These findings suggest that ngrA-dependent antimicrobials besides Xcn and compound F were produced at sufficient levels during preincubation to eliminate S. saprophyticus. X. nematophila produces several NRPS-derived compounds that possess antibiotic activity, including xenematide (33,34), PAX peptides (29,30), and compound C (present study), as well as other NRPS-derived compounds, such as xenotetrapeptide (35), whose activities have yet to be characterized (see Table S1 in the supplemental material). Whether these or other antimicrobial compounds are produced in Grace's medium and either individually or additively suppress the growth of sensitive competitors remains to be determined.…”

Section: Discussionmentioning

confidence: 95%

Role of Secondary Metabolites in Establishment of the Mutualistic Partnership between Xenorhabdus nematophila and the Entomopathogenic Nematode Steinernema carpocapsae

Singh

Orr

Divinagracia

et al. 2015

Appl Environ Microbiol

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bXenorhabdus nematophila engages in a mutualistic partnership with the nematode Steinernema carpocapsae, which invades insects, migrates through the gut, and penetrates into the hemocoel (body cavity). We showed previously that during invasion of Manduca sexta, the gut microbe Staphylococcus saprophyticus appeared transiently in the hemocoel, while Enterococcus faecalis proliferated as X. nematophila became dominant. X. nematophila produces diverse secondary metabolites, including the major water-soluble antimicrobial xenocoumacin. Here, we study the role of X. nematophila antimicrobials in interspecies competition under biologically relevant conditions using strains lacking either xenocoumacin (⌬xcnKL strain), xenocoumacin and the newly discovered antibiotic F (⌬xcnKL:F strain), or all ngrA-derived secondary metabolites (ngrA strain). Competition experiments were performed in Grace's insect medium, which is based on lepidopteran hemolymph. S. saprophyticus was eliminated when inoculated into growing cultures of either the ⌬xcnKL strain or ⌬xcnKL:F strain but grew in the presence of the ngrA strain, indicating that ngrA-derived antimicrobials, excluding xenocoumacin or antibiotic F, were required to eliminate the competitor. In contrast, S. saprophyticus was eliminated when coinjected into M. sexta with either the ⌬xcnKL or ngrA strain, indicating that ngrA-derived antimicrobials were not required to eliminate the competitor in vivo. E. faecalis growth was facilitated when coinjected with either of the mutant strains. Furthermore, nematode reproduction in M. sexta naturally infected with infective juveniles colonized with the ngrA strain was markedly reduced relative to the level of reproduction when infective juveniles were colonized with the wild-type strain. These findings provide new insights into interspecies competition in a host environment and suggest that ngrA-derived compounds serve as signals for in vivo nematode reproduction. Microorganisms employ various strategies to compete for space, nutrients, and other resources (1). In exploitative competition, limiting nutrients are quickly utilized by specific microorganisms without direct interaction between competitors. Interference competition, on the other hand, makes use of direct, antagonistic interactions. We study a tripartite model system in which the pathogenic bacterium, Xenorhabdus nematophila, establishes a mutualistic partnership with an entomopathogenic nematode, Steinernema carpocapsae, that vectors the bacterium into susceptible insect hosts. This tractable model system provides an excellent opportunity to identify biologically relevant competitors and study the role of X. nematophila antimicrobials in interspecies competition in a host environment.Xenorhabdus nematophila exhibits two distinct phases in its life cycle (2-5). It engages in a species-specific mutualistic relationship with S. carpocapsae, where it resides in a specialized region of the anterior intestine of the infective juvenile (IJ) stage of the nematode (6). The IJs invade s...

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“…For example, xenocoumacins [6–8], xenortides [9], xenematides [10] and PAX-peptides [11, 12], which target a broad spectrum of microorganisms, are synthesized by the non-ribosomal peptide synthetase (NRPS) enzymes and polyketide synthase (PKS) enzymes of Xenorhabdus strains. Antagonism with other Xenorhabdus or closely related bacterial genera may also be mediated by ribosomal-encoded bacteriocins [13, 14].…”

Section: Introductionmentioning

confidence: 99%

A New Member of the Growing Family of Contact-Dependent Growth Inhibition Systems in Xenorhabdus doucetiae

et al. 2016

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Xenorhabdus is a bacterial symbiont of entomopathogenic Steinernema nematodes and is pathogenic for insects. Its life cycle involves a stage inside the insect cadaver, in which it competes for environmental resources with microorganisms from soil and the insect gut. Xenorhabdus is, thus, a useful model for identifying new interbacterial competition systems. For the first time, in an entomopathogenic bacterium, Xenorhabdus doucetiae strain FRM16, we identified a cdi-like locus. The cdi loci encode contact-dependent inhibition (CDI) systems composed of proteins from the two–partner secretion (TPS) family. CdiB is the outer membrane protein and CdiA is the toxic exoprotein. An immunity protein, CdiI, protects bacteria against inhibition. We describe here the growth inhibition effect of the toxic C-terminus of CdiA from X. doucetiae FRM16, CdiA-CTFRM16, following its production in closely and distantly related enterobacterial species. CdiA-CTFRM16 displayed Mg2+-dependent DNase activity, in vitro. CdiA-CTFRM16-mediated growth inhibition was specifically neutralized by CdiIFRM16. Moreover, the cdi FRM16 locus encodes an ortholog of toxin-activating proteins C that we named CdiCFRM16. In addition to E. coli, the cdiBCAI-type locus was found to be widespread in environmental bacteria interacting with insects, plants, rhizospheres and soils. Phylogenetic tree comparisons for CdiB, CdiA and CdiC suggested that the genes encoding these proteins had co-evolved. By contrast, the considerable variability of CdiI protein sequences suggests that the cdiI gene is an independent evolutionary unit. These findings further characterize the sparsely described cdiBCAI-type locus.

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Structure elucidation and biosynthesis of lysine-rich cyclic peptides in Xenorhabdus nematophila

Cited by 80 publications

References 14 publications

Attenuated Virulence and Genomic Reductive Evolution in the Entomopathogenic Bacterial Symbiont Species, Xenorhabdus poinarii

Attenuated Virulence and Genomic Reductive Evolution in the Entomopathogenic Bacterial Symbiont Species, Xenorhabdus poinarii

Role of Secondary Metabolites in Establishment of the Mutualistic Partnership between Xenorhabdus nematophila and the Entomopathogenic Nematode Steinernema carpocapsae

A New Member of the Growing Family of Contact-Dependent Growth Inhibition Systems in Xenorhabdus doucetiae

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