Domestication of Chemicals Attacking Metazoan Embryogenesis: Identification of Safe Natural Products Modifying Developmental Signaling Pathways in Human

Overview

Journal J Antibiot (Tokyo)

Specialties Infectious Diseases
Pharmacology

Date 2021 Aug 12

PMID 34381189

Authors

Naoyuki Nishiya

Honami Yonezawa

Affiliations

Soon will be listed here.

Abstract

Soil microorganisms are rich sources of bioactive natural products. Interspecies interactions are the cues of their production and refine biological activities. These interactions in natural environments include the interplay between microorganisms and Metazoans (animals), such as nematodes, insects, and ticks. Chemical intercellular communication modulators could exert ideal Metazoan-selective toxicity for defending microorganisms. Developmental signaling pathways, such as the Notch, TGF-beta, and Wnt pathways, are intercellular communication networks that contribute to the reproducible formation of complex higher-order Metazoan body structures. Natural modifiers of the developmental signaling pathway are attractive therapeutic seeds for carcinoma and sarcoma treatment. However, these fundamental signaling pathways also play indispensable physiological roles and their perturbation could lead to toxicity, such as defects in stem cell physiology and tissue regeneration processes. In this review, we introduce a screening system that selects developmental signaling inhibitors with wide therapeutic windows using zebrafish embryonic phenotypes and provide examples of microorganism-derived Wnt pathway inhibitors. Moreover, we discuss safety prospects of the developmental signaling inhibitors.

References

WAKSMAN S . ANTAGONISTIC RELATIONS OF MICROORGANISMS. Bacteriol Rev. 1941; 5(3):231-91. PMC: 440853. DOI: 10.1128/br.5.3.231-291.1941. View

Davies J, Spiegelman G, Yim G . The world of subinhibitory antibiotic concentrations. Curr Opin Microbiol. 2006; 9(5):445-53. DOI: 10.1016/j.mib.2006.08.006. View

Yim G, Wang H, Davies J . Antibiotics as signalling molecules. Philos Trans R Soc Lond B Biol Sci. 2007; 362(1483):1195-200. PMC: 2435582. DOI: 10.1098/rstb.2007.2044. View

Romero D, Traxler M, Lopez D, Kolter R . Antibiotics as signal molecules. Chem Rev. 2011; 111(9):5492-505. PMC: 3173521. DOI: 10.1021/cr2000509. View

Young I, Crawford J . Interactions and self-organization in the soil-microbe complex. Science. 2004; 304(5677):1634-7. DOI: 10.1126/science.1097394. View

ODonnell A, Young I, Rushton S, Shirley M, Crawford J . Visualization, modelling and prediction in soil microbiology. Nat Rev Microbiol. 2007; 5(9):689-99. DOI: 10.1038/nrmicro1714. View

Quince C, Curtis T, Sloan W . The rational exploration of microbial diversity. ISME J. 2008; 2(10):997-1006. DOI: 10.1038/ismej.2008.69. View

Crawford J, Harris J, Ritz K, Young I . Towards an evolutionary ecology of life in soil. Trends Ecol Evol. 2006; 20(2):81-7. DOI: 10.1016/j.tree.2004.11.014. View

Trevors J . One gram of soil: a microbial biochemical gene library. Antonie Van Leeuwenhoek. 2009; 97(2):99-106. DOI: 10.1007/s10482-009-9397-5. View

10.

Bardgett R, van der Putten W . Belowground biodiversity and ecosystem functioning. Nature. 2014; 515(7528):505-11. DOI: 10.1038/nature13855. View

11.

van den Hoogen J, Geisen S, Routh D, Ferris H, Traunspurger W, Wardle D . Soil nematode abundance and functional group composition at a global scale. Nature. 2019; 572(7768):194-198. DOI: 10.1038/s41586-019-1418-6. View

12.

Crowther T, Boddy L, Hefin Jones T . Species-specific effects of soil fauna on fungal foraging and decomposition. Oecologia. 2011; 167(2):535-45. DOI: 10.1007/s00442-011-2005-1. View

13.

Ferris H . Contribution of nematodes to the structure and function of the soil food web. J Nematol. 2012; 42(1):63-7. PMC: 3380510. View

14.

Hoffmeyer T, Burkhardt P . Choanoflagellate models - Monosiga brevicollis and Salpingoeca rosetta. Curr Opin Genet Dev. 2016; 39:42-47. DOI: 10.1016/j.gde.2016.05.016. View

15.

Fairclough S, Dayel M, King N . Multicellular development in a choanoflagellate. Curr Biol. 2010; 20(20):R875-6. PMC: 2978077. DOI: 10.1016/j.cub.2010.09.014. View

16.

Richter D, King N . The genomic and cellular foundations of animal origins. Annu Rev Genet. 2013; 47:509-37. DOI: 10.1146/annurev-genet-111212-133456. View

17.

Hehenberger E, Tikhonenkov D, Kolisko M, Del Campo J, Esaulov A, Mylnikov A . Novel Predators Reshape Holozoan Phylogeny and Reveal the Presence of a Two-Component Signaling System in the Ancestor of Animals. Curr Biol. 2017; 27(13):2043-2050.e6. DOI: 10.1016/j.cub.2017.06.006. View

18.

Sebe-Pedros A, Irimia M, Del Campo J, Parra-Acero H, Russ C, Nusbaum C . Regulated aggregative multicellularity in a close unicellular relative of metazoa. Elife. 2013; 2:e01287. PMC: 3870316. DOI: 10.7554/eLife.01287. View

19.

Artavanis-Tsakonas S, Rand M, Lake R . Notch signaling: cell fate control and signal integration in development. Science. 1999; 284(5415):770-6. DOI: 10.1126/science.284.5415.770. View

20.

Radtke F, Raj K . The role of Notch in tumorigenesis: oncogene or tumour suppressor?. Nat Rev Cancer. 2003; 3(10):756-67. DOI: 10.1038/nrc1186. View