1. Identification, Taxonomy, Lifestyle, and Diversity of Xenorhabdus spp.
1.1. Their Identification/Taxonomy
As
Xenorhabdus and
Photorhabdus bacteria (Enterobacterales: Morganellaceae) are phylogenetically close, it is not surprising that at first they were of the same genus
[1]. Thus, two bacterial species in this genus (that is,
Xenorhabdus nematophila (type species) and
X.
luminesces) including symbionts of the nematode genera
Steinernema and
Heterorhabditis, respectively, were exclusively present until 1993
[1]. Yet, the important variations in the phenotypic and molecular traits could distinguish
X.
nematophila from
X.
luminesces, leading to the transfer of all symbionts related to
Heterorhabditis into
Photorhabdus as a new genus with the type species
Photorhabdus luminescens [2]. Before splitting into the two genera, some phenotypic features and symbiotic properties were utilized to characterize
Xenorhabdus and
Photorhabdus bacteria as two recognized groups;
P.
luminescens distinctly had a DNA relatedness group unlike all
Xenorhabdus strains with significant variations in phenotypic traits
[3].
Xenorhabdus bacteria are obviously separated from
Photorhabdus species/strains by the 16S rDNA signature sequences
[4]. Yet, both
Photorhabdus luminescens and
X.
nematophila received much research work, due to being type species of their two genera, with high insecticidal activities and a global distribution.
Interestingly, the genus
Xenorhabdus still has more homogenous species than
Photorhabdus, but the former genus possesses a higher number of species than the latter. For example, Sajnaga and Kazimierczak
[5] reported 26
Xenorhabdus spp. versus 19
Photorhabdus spp. This is possibly due to higher number of the current
Steinernema species (the mutualistic partner of
Xenorhabdus spp.) than
Heterorhabditis spp. (the mutualistic partner of
Photorhabdus spp.), i.e., >100
Steinernema spp. but >20
Heterorhabditis spp.
[6]. Admittedly, there are other undescribed species related to both
Xenorhabdus and their
Steinernema partner which are recognized or are likely to become recognized soon. In this respect, the number of their close relatives,
Photorhabdus species, has recently doubled, from four to twenty in the last few years
[7].
1.2. The Lifestyle and Diversity of Xenorhabdus spp.
Basically, the bacterial species in the genus
Xenorhabdus have a mutualistic relationship with the entomopathogenic nematodes (EPNs) of the genus
Steinernema. The bacteria live symbiotically in the specialized intestinal vesicles of
Steinernema. The two partners naturally form an antagonist sharing mainly against their insect hosts. The EPN-third-stage infective juveniles (IJs) conserve the bacteria in their body from the outer environmental stresses until these IJs release them within the insect body. In addition, after EPN infection and depleting the host resources, the IJs vector the bacteria from one susceptible host to another. In turn,
Xenorhabdus spp. generate antimicrobial compounds and secondary metabolites into the insect. These materials can not only kill the insect host and prepare the contents of its body to feed the nematodes for their development and reproduction, but also protect the insect cadaver from soil scavengers and saprobes
[8]. During their feeding, the nematodes also swallow the bacteria in order to grow and reproduce.
Steinernema–bacterial symbiont specificity and their coevolution have been thoroughly studied for many involved axenic (free of bacteria) and monoxenic (having a
Xenorhabdus species)
Steinernema species
[5]. While a
Steinernema species can presumably set up symbiosis with only one species of
Xenorhabdus, any of numerous
Xenorhabdus species are able to associate with several
Steinernema. On the contrary, the symbiotic
Heterorhabditis–
Photorhabdus associations are more adaptable as many species of each partner can engage in symbiotic relationships with multiple species of the other partner
[9]. These facts have recently been reviewed and backed by plenty of data
[10]. However, the mechanisms underlying these relationships remain to be clarified
[5]. These associations do not negate the fact that the robust specificity that favors symbionts with the most useful attributes facilitates effective transfer of such a nematode–bacterium pair from a susceptible insect pest to another. Generally, Sajnaga and Kazimierczak
[5] concluded that there is a possibility of horizontal transfer of
Xenorhabdus bacteria between different
Steinernema species, relying on the species of
Xenorhabdus–
Steinernema pair used. However, such switching in the bacterium–nematode pair may have its pros and cons. On the positive side, associations of
Steinernema species with new
Xenorhabdus partner may validate colonization of novel niches or expand one by offering considerable fitness benefits
[11][12]. These favorable results may occur when the introduced bacteria/symbiont is closely related to its native
Steinernema species. On the negative side, the
Xenorhabdus partner switching frequently has a harmful effect on the
Steinernema host in terms of a reduction in their fitness, reproduction, and symbiont carriage as well as virulence. For example,
Xenorhabdus bovienii is the native symbiotic bacteria of
S.
feltiae. However, using
X.
nematophila strain HGB315, not the native symbiont of
S.
feltiae, this nematode species developed and turned into gravid much faster at approximately 4 days on
X.
bovienii (versus 5–6 days on
X.
nematophila HGB315) post-seeding
[13]. These detrimental outputs are usually associated with non-cognate and phylogenetically distant symbionts
[5]. Eventually, researchers and stakeholders should be aware of the fact that the
Steinernema host diversity substantially impacts coadaptation between various
Xenorhabdus–
Steinernema partners
[14][15] for their further wise application. In this respect, Tailliez et al.
[16] could identify two main groups of
Xenorhabdus strains based on phenotypic analysis. A group included bacterial strains that can commonly grow at 35–42 °C, while the other group included
Xenorhabdus strains that grow below 35 °C. Hence,
Xenorhabdus bacteria may be adapted to temperate, subtropical, or tropical regions. They are also differently impacted by the growth temperature of their
Steinernema host
[16]. Moreover, the wide host range of their nematode host along with their major attributes can prove their diversity and global distribution
[17] as well as give opportunities to familiarize stakeholders with the potential usage of these symbiotic bacteria
[6][8]. With the global spread of the
Steinernema–
Xenorhabdus complex, recent references, e.g.,
[7], still indicate that EPNs are not discovered in Antarctica. The long-established realization regarding the species-specific characterization for the dyad
Steinernema–
Xenorhabdus complex as partners for the mutualism is still effective. Thus, it can bode well for more investigations concerning their distribution in diversity and space
[18]. Moreover, current research efforts have been focusing on optimizing methods and techniques for EPN surveys and extraction
[4][5] to detect novel species/strains that bode well for effective and safe biocontrol of pests and pathogens and adaptation to local conditions. Therefore, it can be mostly presumed that the distribution and diversity of the EPN species is only an artefact of the linked sampling efforts
[7]. However, growing interest is mainly dedicated to these bacteria when applied to suppress pests and pathogens independently, i.e., without the EPN partners
[8][19][20][21][22][23].
Similar to their near relatives,
Photorhabdus species, all the species of
Xenorhabdus are exclusively linked symbionts to the
Steinernema spp.–IJ stage
[2]. The exception of
Photorhabdus, materialized in
P. asymbiotica as a human pathogen in addition to infecting insects
[24], is not found in
Xenorhabdus. None of the
Xenorhabdus bacteria were found in free-living order in nature; therefore, they had formerly boosted doubts concerning their ability to survive and infect pathogens/pests without the EPN partner.
2. Pathogenicity of Xenorhabdus spp.
2.1. Magnitude and Profile of Pathogenicity
Traditionally, various
Steinernema–
Xenorhabdus partnerships, to attack and kill numerous arthropod pests, have been marketed and utilized as biocontrol agents
[6], with increasing ambition for their expansion to prepare them for reliable alternatives in pest management and plant protection
[24][25][26][27][28]. In the original status of the natural
Steinernema–
Xenorhabdus complex,
Xenorhabdus host range is surely limited to the ability of the IJs to locate and infect the host. This is a prerequisite for the development and multiplication of
Xenorhabdus spp. to achieve high levels of cells within the host. Factually, both mutualists,
Steinernema and
Xenorhabdus, can generate bioactive compounds to kill the invaded host
[13][20]. Thereafter, the bacterial cells can modify the insect host tissues to become a nutrient diet needed for the IJ development and multiplication. Hence, the pathogenicity depends on the bacterial activity and growth. Thus, the
Xenorhabdus rate of growth is tightly related to the time needed to kill the insect host. Clearly,
Xenorhabdus spp. are quite virulent pathogens of a broad range of pests/pathogens including insects, fungi, bacteria, protozoa, and nematodes
[20][21].
Discovering the competency of
Xenorhabdus bacteria to live in fresh water and in soil for 6 days has surely opened a new avenue with fixed timeframe for their further biocontrol usages, apart from their mutualistic
Steinernema [27]. Consequently, various formulations and techniques, fundamentally comprising just the bacteria or/and bacterial metabolites, have been used
[6][8][20][21][28][29][30][31][32][33][34]. In this regard, boosted pathogenicity islands of the
Xenorhabdus chromosome, having numerous genes that encode various antibiotics, insecticidal protein toxins, enzymes, and bacteriocins, were investigated
[8][20][35], and more are still to be further characterized, e.g.,
[21][28][36][37]. For instance, only one
Xenorhabdus strain may generate a variety of antifungal and antibacterial compounds. Some of its compounds are active against insects, protozoa, nematodes, and cancer cells, too
[20]. All tested
X.
nematophila strains showed insecticidal activity against representative pests of three insect orders; the cabbage white caterpillar
Pieris brassicae (Lepidoptera: Pieridae), the mosquito larva
Aedes aegypti (Diptera: Culicidae), and the mustard beetle
Phaedon cochleariae (Coleoptera: Chrysomelidae)
[34]. In this study and others
[19][23][38][39], an important note is the variation in the abilities of different
Xenorhabdus species/strains to kill/inhibit the growth of the intended pest or pathogen. These variations are based either on the ability of each
Xenorhabdus species/strain to generate effective metabolites or the relative susceptibility/tolerance of the targeted pest/pathogen. These differences are found not only between
Xenorhabdus species/strains, but surely exist to varying degrees between bacterial species/strains belonging to different genera.
An obvious technique to circumvent the lack of appropriate efficacy of
Xenorhabdus species/strain and/or to increase its potency is to introduce other antagonists in combination with
Xenorhabdus bacteria and/or their bioactive compounds. This approach can establish and boost the efficacy of the introduced organism, too. Clearly, synergistic activity to kill the beet army worm
Spodoptera exigua could be obtained by mixing growth media supernatants of
Xenorhabdus bacteria with
B. cereus or
B. thuringiensis spores. In this case, while the supernatant of
Xenorhabdus bacteria could exert its impact on the insect hemocoel, the
Bacillus cells were able to perforate the insect midgut epithelium
[40][41]. Later, Eom et al.
[41] could develop a “dual Bt-plus” product by mixing
B. thuringiensis (Bt) spores and culture broth of
X. nematophila (Xn). Although this product demonstrated high toxicity, it has also some modification to widen its efficacy against a diverse insect pest spectrum. Their tests centered on increasing “Bt-Plus” toxicity against a semi-susceptible insect,
S.
exigua, via adding Xn metabolites. Given the fact that Xn metabolites, benzylideneacetone (BZA) and oxindole (OI), can boost the Bt insecticidal activities, adding each of them (OI or BZA) could significantly enhance Bt-Plus pathogenicity. Moreover, when the freeze-dried Xn culture broth was included into Bt-Plus, a much smaller amount could suffice to raise the toxicity relative to the amount of BZA or OI. High-performance liquid chromatography analysis revealed that there were more than 12 unidentified
X.
nematophila metabolites in Xn culture broth. Therefore, they
[41] proposed that there are other potent biological response modifiers in
X.
nematophila metabolites, not solely OI and BZA. Likewise, a
Xenorhabdus species could induce high mortality of
S. exigua third-instar larvae but its pathogenicity was much less for the fifth-instar larvae. Seongchae and Yonggyun
[42] speculated that the high mortalities in the third-instar larvae were due to antibiotic activity against
B. cereus, a gut symbiont needed to optimize
S. exigua development. To enhance the
Xenorhabdus species pathogenicity in the fifth instar, the bacteria should be delivered into the hemocoel. Thus, the authors utilized
B. thuringiensis aizawai (
Bt) as a synergist to back entry of the bacteria from the insect gut lumen into its hemocoel by disrupting the
S. exigua gut epithelium. As a result, the applied bacterial mixture was highly synergistic against the
S. exigua fifth-instar larvae. This synergism was proved via the successful infection of
X. sp. or
Bt in the insect hemocoel. Therefore,
Xenorhabdus bacteria can be used to kill
S. exigua by oral treatment in a mixture with
Bt [42].
Usually, re-extraction of the
Xenorhabdus bacteria from the insect cadavers and comparison with the standard (original) culture can assure Koch’s postulates
[20][43]. Although the obtained data confirmed the direct toxicity of the bacteria to definite insect species in nature, e.g.,
[8][34][43], particular
Xenorhabdus bacteria may have wide host range of insect pests. For example, 122 strains of symbiotic bacteria associated with 23 EPNs were gathered from various Chinese localities
[44]. These extracted strains displayed oral growth inhibition and/or insecticidal activity against the
Ostrinia furnacalis larvae. One of the strains, however,
Xenorhabdus sp. SY5, with determined partial toxin gene sequence, exhibited strong insecticidal activity to a variety of economically significant agricultural pests. Their species comprised
Plutella xylostella,
Ostrinia furnacalis,
Tenebrio molitor,
S. exigua, and
Mythimna separata. The strain isolated from
Steinernema sp. SY5 appeared to have seven purified toxins based on DEAE-52 column chromatography. These toxins exhibited, to a certain extent, growth inhibition and/or insecticidal activity to these insect species. The authors
[44] stressed the high virulence of this strain as a potential asset for biological pest control.
It is likely that the arsenal of
Xenorhabdus spp. still possesses much that has not been discovered yet, for controlling wide categories of many pathogens. In this respect, Hajihassani et al.
[45] assessed the efficacy of application timing, that is, 5 days before planting (DBP) and at planting (AP) of
X. bovienii and
X. szentirmaii metabolites for the root-knot nematode (RKN)
Meloidogyne incognita control on cabbage roots in two environmental conditions. At-plant applications of
Paecilomyces lilacinus strain 251 (MeloCon WG) and secondary metabolites of
Burkholderia rinojensis strain A396 (Majestene) and oxamyl (Vydate) were used for comparison. In the greenhouse,
X. szentirmaii and Vydate at 5 DBP had a lower (
p < 0.05) root gall rating than the untreated control. Vydate and all metabolite treatments showed significantly lower root galling relative to Majestene, MeloCon, and the control. In addition, the metabolites and Vydate decreased (
p < 0.05) RKN egg counts per gram of root compared to the other treatments in the greenhouse. No differences were observed in the egg count between Vydate and the metabolites. At-plant and 5 DBP applications of
X. bovienii and
X. szentirmaii at decreased the total egg count relative to Majestene and the control in the greenhouse. Thus, the natural metabolites generated by the two
Xenorhabdus species can control
M.
incognita regardless of application timing and are suggested as a potential alternative to nematicides in organic production systems
[45]. In addition, direct effect of
X. lircayensis, identified using the whole genome, was evaluated on a population of the plant-parasitic nematode
Xiphinema index [46]. Supernatants of bacteria were discarded via centrifugation, then
X.
lircayensis were resuspended in phosphate-buffered saline (PBS) and set to 1 × 10
6 and 1 × 10
7 CFU mL
−1 for laboratory and semi-field assays, respectively. Cell bacteria (1 × 10
7 CFU mL
−1) were applied in the semi-field assay by 30 min dipping grapevine roots in the bacterial suspension. Afterward, these plants were established in 5 L pots filled with naturally
X.
index-infested soil and immediately inoculated with 350 mL of the same
X.
lircayensis suspension. The nematicidal effects of
X.
lircayensis suspension appeared at 24 h post-inoculation but attained full (100%)
X. index mortality after 72 h exposition (
p < 0.001) in laboratory assays. In addition, under semi-field conditions,
X.
lircayensis suspension significantly (
p ≤ 0.05) reduced
X. index populations. While the study recommended
X.
lircayensis as a good candidate for further assesses in field conditions, additional analyses must be performed to set the metabolites, enzymes, and mode of action for its nematicidal aptitude
[46]. Vicente-Díez et al.
[47] tested the antibiotic impact of cell-free supernatants (CFSs) and unfiltered ferments (UFs) of
X. nematophila and
P. laumondii on another plant pathogenic category represented by the fungus
Botrytis cinerea growth and compared the activity of bacteria isolated from a bio-fermenter with the commercial
B. amyloliquefaciens (Serenade
®ASO, Bayern CropScience). The UF and CFS of
X. nematophila suppressed about 95% and 80% of
B.
cinerea growth, respectively, while both UF and CFS of
P. laumondii inhibited only about 40%. These data showed the potential of CFS and UF of
X. nematophila for
B. cinerea control.
In another study
[48],
X. bovienii metabolite treatment was comparable to fenbuconazole (a commercial fungicide) in decreasing
Fusicladium effusum sporulation on pecan (
Carya illinoinensis) terminals.
X. bovienii metabolite and broth treatments suppressed development of lesions brought about by
Phytophthora cactorum (using pecan tree leaves maintained on agar). The bacterial metabolite treatment was also toxic to
Armillaria tabescens, another important pathogen but of peach (
Prunus persica) trees, especially in the southeastern United States
[48]. These results offer a basis for further investigations on utilizing the bacterial metabolites or broth for suppression of economically significant diseases of pecan and peach. Likewise,
X.
nematophila generates many metabolites during growth and multiplication. Only one of these secondary metabolites (xenocoumacin 1) proved to have a robust antifungal activity for controlling
Rhizoctonia solani [49],
Botrytis cinerea [50],
Alternaria alternate [51], several
Phytophthora species, etc.
[50][51][52][53]. These effects suggest, a priori, that other
Xenorhabdus species, which are available or are likely to befit broadly soon, are able to control other pests and diseases. Recently,
Xenorhabdus budapestensis strain C72 showed remarkable suppressing effect on spore germination and mycelial growth of the fungus
Bipolaris maydis which causes the Southern corn leaf blight
[54]. The relative control effect of the bacterial cell-free culture media reached 59.15% and 77.96% in greenhouse and field experiments, respectively, which was as efficacious as a commercial fungicide. The in vitro tests also indicated that C72 cell-free culture media with thermostability proved wide-spectrum antifungal efficacy towards other economically significant fungi and pathogens of plants
[54]. Chacón-Orozco et al.
[55] reported that among 16 strains of EPN-symbiotic bacteria, cell-free supernatants of
X.
szentrimaii had the highest fungicidal effect on mycelium growth of
Sclerotinia sclerotiorum. They reported that
X.
szentrimaii produces volatile organic compounds that inhibit
S.
sclerotiorum growth and/or its consequent generation of sclerotia.
The discovery and cloning of additional useful compounds from
Xenorhabdus are still in progress
[22][36][37][56][57]. Factually, these bacteria can demonstrate metabolites with the major characteristics of safe pesticides. In other words, their effect is boosted with an enhanced dose, but a negative correlation is found between the number or density of pathogen/pest eggs, adult survival of the pest, percentage of hatching, and the
Xenorhabdus bacterial dosage
[8][20][21].
2.2. Xenorhabdus Bacterial Mechanism via Their Secreted Materials
The
Xenorhabdus bacteria are typically famous for killing their hosts via toxemia/septicemia, within the form of the normal
Xenorhabdus–
Steinernema complex
[8]. However, as different
Steinernema species carrying specific
Xenorhabdus strains can invade a single insect,
Xenorhabdus spp. are also engaged in competition with both related strains and nonrelated gut microbes of the insect host
[58]. This competition, in addition to
Xenorhabdus having the capability to kill the insect host, can explain why
Xenorhabdus spp. produce a treasure trove of diverse insecticidal and antimicrobial compounds. Moreover, Ciezki
[58] found that
X.
bovienii and
X.
nematophila can generate R-type bacteriocins (xenorhabdicins) that are specifically active towards different
Xenorhabdus and
Photorhabdus species. The latter author stressed that xenorhabdicin activity could be predictive of competitive results between two
Xenorhabdus strains, while other determinants, besides xenorhabdicins, were mainly included in the competitive success between the other
Xenorhabdus strains. Thus, Ciezki
[58] demonstrated that various
Xenorhabdus antibiotics could define the output of interspecies competition in a natural host environment.
The mounting ambition to harness
Xenorhabdus-derived compounds in industrial products stems from not only their abundance, but also their qualities that enhance their functions. Initially, standalone pathogenicity trials of
Xenorhabdus bacteria and/or their released materials usually start with their direct injection into the haemocoel of insects via artificial means
[8][43].
Xenorhabdus protein toxins ordinarily have oral or/and injectable toxicity to insects.
Xenorhabdus-derived compounds have a variety of modes of action that have been reviewed
[20][46][58]. The suggested mode of action of
Xenorhabdus–dithiopyrrolone derivatives (comprising the two metabolites xenorhabdins and xenorxides) is inhibition of RNA synthesis
[59]. However,
Xenorhabdus–indole-containing compounds could show additional mechanism via weak phospholipase A2 inhibitory effects. This latter, phospholipase A2, is necessary for producing eicosanoids. Eicosanoids have substantial role for activating the insect-immune response via mediating and modulating hemocyte behavior
[60]. Thus, Dreyer et al.
[20] assumed that indole-containing materials produced by
X.
nematophila can suppress the immune response of the insect host to be more vulnerable to microbial infection.
Xenorhabdus budapestensis has two antimicrobial peptides, GP-19 and EP-20, with wide-spectrum antimicrobial activity against bacteria and fungi
[61]. The first peptide, with a neutral charge, is suggested to cause a disruptive impact to the host membrane by moving to the cell surface and penetrating the membrane. The second peptide likely has a different mode of action. It is suggested to have an intracellular influence, by inhibiting protein synthesis, cell wall, and nucleic acid
[61].
Complete genome sequencing of various
Xenorhabdus species/strains has been uncovering the ability of these bacteria to produce numerous secondary metabolites. Thus, it can contribute to comprehensive examination of the molecular basis underlying the biological control activity of this
Xenorhabdus strain
[62]. Various types of biological molecules have been detected and characterized for
Xenorhabdus bacteria. The main antimicrobial materials comprise ribosomal-encoded benzylideneace-tone
[63] xenocin and bicornutin
[64][65], and non-ribosomally generated xenematides
[66], fabclavines
[67], xenocoumacin
[68], nematophin
[69], rhabdopeptides
[70], and peptide–antimicrobial–
Xenorhabdus lipopeptides
[71]. Knowing the attributes of these compounds, e.g., the range of pH and heating needed for their stability, should enable their successful use as alternatives to chemical pesticides in agriculture
[19][20]. For example, depsipeptides are peptides that generally have alternating peptide and ester bonds, and five classes of depsipeptides have been characterized. The first class, produced by
Xenorhabdus doucetiae and
X. mauleonii and known as xenoamicin, are tridecadepsipeptides with hydrophobic amino acids
[72]. The genome sequence of
X. doucetiae DSM 17909 revealed that xenoamicins are encoded by five non-ribosomal peptide synthetases (NRPSs), XabABCD, and an aspartic acid decarboxylase (XabE). Due to its hydrophobic characteristics, xenoamicin can interact with the host–cytoplasmic membrane. Nevertheless, no antifungal or antibacterial activity has been listed for xenoamicin A, which displays a different mechanism. Xenoamicin A has weak cytotoxic and anti-protozoal activities
[72]. The second class of depsipeptides, the lipodepsipeptides produced by
X. indica, has supplemental fatty acid chain linked to one of the amino acids
[73]. The peptides are named after their amino acid sequence and are known as taxlllaids (A–G). Natural taxlllaid A and synthetic taxlllaids B–G can manifest antiprotozoal activity. Taxlllaid A is optimistically cytotoxic to human carcinoma cells
[73]. The third depsipeptides class are grouped as indole-containing xenematides. Xenematide A, secreted by
X.
nematophila [74], is antibacterial and insecticidal. The other two depsipeptide classes contain szentiamide and xenobactin isolated from
X.
szentirmaii and
Xenorhabdus sp., strain PB30.3
[75][76]. Both compounds are active against
Plasmodium falciparum (protozoan parasite of humans) and have some activity against
Trypanosoma brucei rhodesiense and
Trypanosoma cruzi (parasites of many vertebrates). Szentiamide possesses a weak cytotoxic activity against
Galleria mellonella hemocytes. Xenobactin has no cytotoxic activity; yet, it is active against
Micrococcus luteus. This antibacterial activity is mostly due to its hydrophobic status where it probably targets the bacterial cell membrane
[19]. Eventually, each of the aforementioned groups of toxins has a conceivable role as a biocontrol material, via a particular mode of action against pathogens and arthropod pests such as vector insects. The differential virulence of the candidate toxins can be correlated not only with their interspecies/strain gene sequence diversity of the same EPN-symbiotic bacterial genus but also between the two EPN-symbiotic bacterial genera,
Xenorhabdus and
Photorhabdus [33][55]. Fabclavine is broadly generated in
Xenorhabdus species but
Photorhabdus species do not produce fabclavines, except for
P. asymbiotica [77]. This can elucidate partially why the tested
Photorhabdus species (
P.
kayaii,
P.
namnaoensis,
P.
laumondii,
P.
akhurstii,
P.
thracensis) did not show antiprotozoal activity
[33]. On the contrary, fabclavines 1a and 1b demonstrate diverse bioactivities against various bacterial, fungal, and protozoal organisms
[68]. Other antiprotozoal bioactive materials produced by 22
Xenorhabdus species are xenorhabdins, xenocoumacins, and PAX peptides. Thus, the tested
Xenorhabdus species were more effective against the serious human protozoal parasites
Entamoeba histolytica,
Acanthamoeba castellanii,
Trichomonas vaginalis,
Trypanosoma cruzi, and
Leishmania tropica [33]. Furthermore, it is quite possible that more
Xenorhabdus-derived toxins will uncover certain variations among bacterial strains regarding toxicity to these pests. Various features and details concerning the mode of action, structure, and putative function of the
Xenorhabdus-bioactive compounds in the process of infection have been clarified
[20][21][58].
Xenorhabdus bacteria can control economically significant endoparasitic species of nematodes inside plant roots via their antibiotic compounds and toxins
[78]. Moreover, the bacterium-derived protease inhibitor protein could be genetically transformed into tobacco plants in order to offer protection from the aphids
Myzus persicae [31]. Therefore, such genetically engineered techniques are suggested as a promising replacement to the Bt toxin
[7], to preclude development of insect resistance
[56]. The numerous instances of pathogen and arthropod pest killing induced by
Xenorhabdus spp.
[8][21][25][36][37][61][78] do not deny the variations in the immune response among their pathogen/pest hosts
[33][34][36][79]. In addition, the difference in immune reaction among host species/strains may be based on biologic/genetic and evolutionary/ecological factors set for each pathogen–host system. The various system constituents, including specificity, induction, and memory of the immunity, can determine the cognate resistance mechanism of the intended insect population/species
[80]. Generally, physical parameters, especially pH, temperature, and sodium chloride, could variably affect the mortality percentage induced by these metabolites to the
G.
mellonella larvae
[81].