Novel Prodiginine Derivatives Demonstrate Bioactivities on Plants, Nematodes, and Fungi

Abstract

Bacterial metabolites represent an invaluable source of bioactive molecules which can be used as such or serve as chemical frameworks for developing new antimicrobial compounds for various applications including crop protection against pathogens. Prodiginines are tripyrrolic, red-colored compounds produced by many bacterial species. Recently, due to the use of chemical-, bio-, or mutasynthesis, a novel group of prodiginines was generated. In our study, we perform different assays to evaluate the effects of prodigiosin and five derivatives on nematodes and plant pathogenic fungi as well as on plant development. Our results showed that prodigiosin and the derivatives were active against the bacterial feeding nematode Caenorhabditis elegans in a concentration- and derivative-dependent manner while a direct effect on infective juveniles of the plant parasitic nematode Heterodera schachtii was observed for prodigiosin only. All compounds were found to be active against the plant pathogenic fungi Phoma lingam and Sclerotinia sclerotiorum. Efficacy varied depending on compound concentration and chemical structure. We observed that prodigiosin ( 1 ), the 12 ring- 9 , and hexenol 10 derivatives are neutral or even positive for growth of Arabidopsis thaliana depending on the applied compound concentration, whereas other derivatives appear to be suppressive. Our infection assays revealed that the total number of developed H. schachtii individuals on A. thaliana was decreased to 50% in the presence of compounds 1 or 9 . Furthermore, female nematodes and their associated syncytia were smaller in size. Prodiginines seem to indirectly inhibit H. schachtii parasitism of the plant. Further research is needed to elucidate their mode of action. Our results indicate that prodiginines are promising metabolites that have the potential to be developed into novel antinematodal and antifungal agents.

Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117

“…On the other side, the nematocidal activity of PG was reported for juvenile Meloidogyne incognita J2 species, harmful on black pepper, with an IC 50 value of 0.2 mg/mL [71], for juveniles of Radopholus similis with LC 50 83 µg/mL and Meloidogyne javanica with the LC 50 value of 79 µg/mL, also exhibiting an antagonistic effect on nematode egghatching ability [72]. Effectiveness of PG against Heterodera schachtii J2 was found to be 4.30 µg/mL [70]. Notably, these values are comparable to IC 50 (Table 1) which may hinder PG application in the agriculture.…”

“…In line with our findings, toxicological assessment of PG obtained from S. marcescens in C. elegans showed no significant toxic activity [69], which suggested the safe use of PG in eukaryotic system. Furthermore, PG and its five derivatives, one with an unsaturated hydroxylated chain on C-ring of PG, and four with various cyclic alkyl substituents (C 4 , C 5 , C 6 , and C 10 ) on the C-ring, and the structures of derivatives were decisive against the C. elegans first stage juveniles [70], with PG exhibiting the highest activity with an EC 50 value of 0.04 µg/mL, while for the synthetic derivatives of PG, no reliable EC 50 could be determined, as the mortality at the highest tested concentration did not exceed 33%. These findings, similar to ours, suggest that some synthetic PG derivatives may not prove to be toxic C. elegans.…”

One Health Probiotics as Biocontrol Agents: One Health Tomato Probiotics

“…Biotechnological processes related to bacteria make it possible to obtain many valuable chemical compounds. For example, bacterial metabolites may be a potential source of bioactive molecules, such as tripyrrolic, red-colored prodiginines, which not only have antimicrobial activity against plant pathogens but also have antinematodal activities [ 38 ]. The combined use of modern molecular genetic methods and toolsets, enzyme engineering, as well as biocatalysts and bioinformatics, make it possible to obtain many natural plant antimicrobial compounds [ 39 ].…”

Optimized prodigiosin production with Pseudomonas putida KT2440 using parallelized noninvasive online monitoring

“…The bright red‐colored natural product prodigiosin is a prominent member of the prodiginine class and is produced by various bacteria, including Serratia marcescens ( S. marcescens ) and Hahella chejuensis ( H. chejuensis ) 1–4 . Prodiginines exhibit various biological activities as antibiotic and antimalarial compounds, anti‐cancer compounds, autophagy modulating compounds, and compounds against plant pathogenic nematodes and fungi 5–12 . Hence the prodiginine prodigiosin is of significant interest for novel drug development 13 …”