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The repeated and improper use of antibiotics had led to an increased number of multiresistant bacteria. Therefore, new lead structures are needed. Here, the synthesis and an expanded structure–activity relationship of the simple and antistaphylococcal amide nematophin from Xenorhabdus nematophila and synthetic derivatives are described. Moreover, the synthesis of intrinsic fluorescent derivatives, incorporating azaindole moieties was achieved for the first time.

This study was conducted to purify and identify metabolites of antimicrobial activity against phytopathogens from Xenorhabdus nematophila YL001. Three dipeptide compounds were purified from its cell-free cultural broth and identified as (±)-nematophin, cyclo (L-Pro-Gly), and N, N′-dimethyl-cyclo (L-Phe-L-Leu). Nematophin demonstrated a wider antifungal spectrum than the other two compounds. It also exhibited strong inhibitory effects on mycelial growth of Rhizoctonia solani and Phytophthora infestans with EC50 values of 40.00 and 51.25 μg/ml, respectively. Its (S)-configuration structure [(+)-nematophin] was also synthesized and exhibited higher antimicrobial activity than the enantiomeric mixture. The detached leaf assay revealed that nematophin possessed significant preventive and curative efficacy against R. solani on broad bean leaves showing corresponding control efficacies of 93.01 and 94.93% at 1,000 μg/ml, comparable to those of a chemical fungicide (carbendazim) at 500 μg/ml. Additionally, the pot experiments indicated that nematophin could effectively inhibit the disease extension on rice and broad bean plants caused by R. solani. Nematophin also exerted some adverse influences on the sclerotial development of R. solani by dramatically suppressing their formation and maturation at 40.00 μg/ml, as well as their germination at 15.00 μg/ml. Morphological and ultrastructural observations showed that the hyphae of R. solani became twisted, shriveled, and deformed at the growing points after exposure to nematophin at 40.00 μg/ml, and that the subcellular fractions also became abnormal concurrently, especially the mitochondrial structure. These results indicate that nematophin has great potential to be used as a bio-pesticide in agricultural production.

This study was conducted to purify and identify metabolites of antimicrobial activity against phytopathogens from Xenorhabdus nematophila YL001. Three dipeptide compounds were purified from its cell-free cultural broth and identified as (±)-nematophin, cyclo (L-Pro-Gly), and N , N′ -dimethyl- cyclo (L-Phe-L-Leu). Nematophin demonstrated a wider antifungal spectrum than the other two compounds. It also exhibited strong inhibitory effects on mycelial growth of Rhizoctonia solani and Phytophthora infestans with EC50 values of 40.00 and 51.25 μg/ml, respectively. Its (S)-configuration structure [(+)-nematophin] was also synthesized and exhibited higher antimicrobial activity than the enantiomeric mixture. The detached leaf assay revealed that nematophin possessed significant preventive and curative efficacy against R. solani on broad bean leaves showing corresponding control efficacies of 93.01 and 94.93% at 1,000 μg/ml, comparable to those of a chemical fungicide (carbendazim) at 500 μg/ml. Additionally, the pot experiments indicated that nematophin could effectively inhibit the disease extension on rice and broad bean plants caused by R. solani. Nematophin also exerted some adverse influences on the sclerotial development of R. solani by dramatically suppressing their formation and maturation at 40.00 μg/ml, as well as their germination at 15.00 μg/ml. Morphological and ultrastructural observations showed that the hyphae of R. solani became twisted, shriveled, and deformed at the growing points after exposure to nematophin at 40.00 μg/ml, and that the subcellular fractions also became abnormal concurrently, especially the mitochondrial structure. These results indicate that nematophin has great potential to be used as a bio-pesticide in agricultural production. [ABSTRACT FROM AUTHOR]

Aims: The role of antibiotics produced by bacterial symbionts of entomopathogenic nematodes is to suppress growth of microbes in the soil environment. These antibiotics are active against Gram-positive and Gram-negative bacteria, and were tested against mastitis isolates from dairy cows. Methods and Results: Two bioassays were adapted for Xenorhabdus antibiotics; an overlay method on agar plates, and serially diluted, cell-free, Xenorhabdus cultures. The antimicrobial activities of the liquid cultures of 13 strains from five Xenorhabdus species were further evaluated. Antimicrobial activities of the type strains of X. nematophila, X. budapestensis and X. szentirmaii were tested on mastitis isolates of Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae with both bioassays. A previously reported antibiotic from X. nematophila, nematophin, was synthesized in three steps from tryptamine and 4-methyl-2-oxovaleric acid sodium salt. Conclusions: The antibiotics of all three Xenorhabdus strains were powerful in either bioassay, but the sensitivity of the isolates differed from each other. While Kl. pneumoniae was the least susceptible, Staph. aureus had the highest sensitivity to each Xenorhabdus strain. Xenorhabdus szentirmaii and X. budapestensis were more potent antibiotic producers than X. nematophila, and raceme nematophin was ineffective against all mastitis isolates. Significance and Impact of the Study: These results indicate that Xenorhabdus antibiotics are effective against mastitis isolates and should be further evaluated for their potential in mastitis control or prevention. [ABSTRACT FROM AUTHOR]

The repeated and improper use of antibiotics had led to an increased number of multiresistant bacteria. Therefore, new lead structures are needed. Here, the synthesis and an expanded structure-activity relationship of the simple and antistaphylococcal amide nematophin from Xenorhabdus nematophila and synthetic derivatives are described. Moreover, the synthesis of intrinsic fluorescent derivatives, incorporating azaindole moieties was achieved for the first time.