Antiprotozoal activity of different Xenorhabdus and Photorhabdus bacterial secondary metabolites and identification of bioactive compounds using the easyPACId approach

Abstract

Natural products have been proven to be important starting points for the development of new drugs. Bacteria in the genera Photorhabdus and Xenorhabdus produce antimicrobial compounds as secondary metabolites to compete with other organisms. Our study is the first comprehensive study screening the anti-protozoal activity of supernatants containing secondary metabolites produced by 5 Photorhabdus and 22 Xenorhabdus species against human parasitic protozoa, Acanthamoeba castellanii, Entamoeba histolytica, Trichomonas vaginalis, Leishmania tropica and Trypanosoma cruzi, and the identification of novel bioactive antiprotozoal compounds using the easyPACId approach (easy Promoter Activated Compound Identification) method. Though not in all species, both bacterial genera produce antiprotozoal compounds effective on human pathogenic protozoa. The promoter exchange mutants revealed that antiprotozoal bioactive compounds produced by Xenorhabdus bacteria were fabclavines, xenocoumacins, xenorhabdins and PAX peptides. Among the bacteria assessed, only P. namnaoensis appears to have acquired amoebicidal property which is effective on E. histolytica trophozoites. These discovered antiprotozoal compounds might serve as starting points for the development of alternative and novel pharmaceutical agents against human parasitic protozoa in the future.

Identification of Fcl-29 as an Effective Antifungal Natural Product against Fusarium graminearum and Combinatorial Engineering Strategy for Improving Its Yield

“…szentirmaii showed no suppressive ability to T. vaginalis and Trypanasoma cruzi, while being effective against Acanthamoeba castellanii and Leishmania tropica . The diverse fabclavine derivatives accompanied with different bioactivity provided a rich resource for biopesticide and medicinal development.…”

“…Additionally, the fabclavines produced by X. szentirmaii showed no suppressive ability to T. vaginalis and Trypanasoma cruzi, while being effective against Acanthamoeba castellanii and Leishmania tropica. 29 The diverse fabclavine derivatives accompanied with different bioactivity provided a rich resource for biopesticide and medicinal development. The fabclavine derivative Fcl-29 identified in XBD14 displayed broad-spectrum antifungal activity against the plant pathogens (Figure S1), thus holding great potential to be developed as new biofungicide applied in the field of plant protection.…”

“…Particularly, Xcn1 showed strong inhibition effects against the mycelial growth of P. infestans. − Fabclavines are a group of peptide–polyketide polyamino hybrids produced by Xenorhabdus spp., and showed a wide-spectrum activity against fungi, bacteria, and protozoa. ,,, Peptide-antimicrobial-Xenorhabdus (PAX) peptides, a kind of lysine-rich cyclic peptides produced by X. nematophila, display broad antimicrobial activity. , Another NP named cabanillasin, showing good activity against different yeasts and filamentous fungi, was isolated from X.…”

Xenorhabdus spp.: An Overview of the Useful Facets of Mutualistic Bacteria of Entomopathogenic Nematodes

“…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 [48]. Consequently, various formulations and techniques (Figure 1), fundamentally comprising just the bacteria or/and bacterial metabolites, have been used [2,4,5,11,17,41,42,[49][50][51][52]. 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 [5,41,53], and more are still to be further characterized, e.g., [22,42,49,54].…”

“…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 [51,78]. Fabclavine is broadly generated in Xenorhabdus species but Photorhabdus species do not produce fabclavines, except for P. asymbiotica [98].…”