LIFE SCIENCE

Scientists found that clams secrete erythromycin to build immune “armor”


Synthesis of erythromycin in mantle membrane Photo courtesy of the research group

On November 29, the Proceedings of the National Academy of Sciences published the latest research results of Liu Baozhong, a researcher at the Institute of Oceanography of the Chinese Academy of Sciences. Liu Baozhong’s research group discovered for the first time that buried shellfish clams can synthesize, store and secrete endogenous erythromycin in specific cells in the body, breaking the existing knowledge that only actinomycetes can synthesize erythromycin, based on this discovery, a new strategy for buried shellfish to adapt to the environment and resist microbial infection was proposed.

After the paper was published, the journal Science reported on the study as soon as possible.

A frequently asked question in nature is how can invertebrates, especially those that live in habitats such as shallow mudflats abundant with microbes, cope with a pathogen-dense environment and survive normally without a specific immune system? Have they evolved defense mechanisms other than the known innate immune system?

The research team has systematically discovered and given a new answer to this question by systematically discovering and giving a new answer to this question: that is, chemical defenses combined with mucus barriers, such as erythromycin synthesis, together with the innate immune system composed of shellfish cells and humoral immunity, constitute its immune “armor” to cope with specific environments.

Erythromycin is a highly effective antimicrobial compound that was previously thought to be produced only by bacteria. In the transcriptome analysis of the mantle membrane of clams, researchers were surprised to find the key gene in the synthesis process of erythromycin – erythromylide synthase gene (MpES).

Researchers first determined the presence of erythromycin in the mantle tissue of the clam by chromatography-mass spectrometry, and then, using transmission electron microscopy, immunohistochemistry and other means, the specific structure of erythromycin produced and stored in the mantle membrane was further localized and characterized as a mucin-like cell, and erythromycin can be secreted in vitro with mucus. The results of antibacterial test confirmed that mucus had antibacterial activity, while knocking down the MpES gene affected erythromycin synthesis in vivo.

Genetic analysis showed that the genotype isolation ratio of MpES in the family parents and offspring of the clam family conformed to Mendelian’s law of separation, which supported the animal-derived nature of erythromycin synthesis genes. Phylogenetic analysis and collinear analysis of genomic regions also suggest that the gene originated in animal lineages.

In addition, erythromycin synthesis has been detected in the same cells of a related species of the genus Clams, suggesting that the ability to produce antibiotics may be more widely present in marine invertebrates, providing an example of the convergent evolution of animal-bacterial secondary metabolites.

The findings provide new insights into the mechanisms of environmental adaptation and immune defense in invertebrates, as well as healthy farming and resistance breeding of economic shellfish.

This paper is another important research result published in PNAS after the team reported the dorsoventral isolation and expression law of shellfish Hox gene in PNAS in 2020. Yue Xin, an associate researcher at the Institute of Oceanography, is the first author of the paper, and Carnegie Institution professors Margaret McFall-Ngai and Liu Baozhong are the corresponding authors.

The research was jointly funded by the National Key Research and Development Program, the Modern Agricultural Industrial Technology System Post Scientist Project of the Ministry of Agriculture, and the Qingdao Marine Science and Technology Pilot National Laboratory Project. (Source: Science in China, Liao Yang, Li Hezhao)

Related paper information:https://doi.org/10.1073/pnas.2214150119



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