hliu092 发表于 2021-1-27 17:00:52

Metabolomics(2): the specificity of host-pathogen interactions/新陈代谢组学之二

This is the article 14 in the theme 'Environmental Physiology/环境生理学' of Journal of Environment and Health Science.

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hliu092 发表于 2021-1-27 17:02:23

The specificity of host-pathogen interactions with emphasis on the specific inhibitor protease synthesized in the invasion-defense process.

Author: Liu Huan, MSc (First Class Honours), The University of Auckland.

Key viewpoints:
This article presents novel theory analyzing the electrophoretic bands between different isozyme species. A matrix is designed in my previous article to make the electrophoretic bands comparable across different isozyme species for PCA analysis. However, the related theory underlying the matrix calculation is discussed in this article below: A locus in DNA / gene molecule should be defined as the proportion of a specific gene sequence segment to the total information of the whole genome, rather than as a specific physical position in the whole genome, which is more accurate. Gene mutation at a certain locus is defined as the gene sequence alteration at a specific physical position in the genome, which is not accurate. PCR electrophoresis is a reflection of the relative molecule mass among various gene sequences. Therefore, the relative position of a specific PCR electrophoresis band is not only a reflection of its quantitative gene among all the gene sequences tested in this experiment, but also a reflection of the proportion of the specific gene sequence information to the total information of all gene sequences tested in this experiment. Correspondingly, the electrophoretic bands in the electrophoretogram also reflect the relative molecular weight of the enzyme molecules expressed by different quantitative genes tested in this experiment. The electrophoretic bands at the same locus are also comparable among different isozyme species of an individual. The electrophoretic bands on the same locus among different isozyme species are just the reflection of different gene sequences with the same quantitative gene status (or the same proportional gene information to the total gene information tested in a experiment). In this article, original viewpoints of specificity on the interactions between host and pathogens are presented on the basis of reviewing materials over a broad range of biological phyla.


1.Pathogen S. aureus VS. Human
Staphylococcal aureus complement inhibitor (SCIN) of protein was discovered . SCIN infects a broad range of animal species, including horses, humans, pigs, which is evolved into strong adaptiveness through genome modification (such as by gene communications with external genetic segments aiming to host-invasion interactions). For the human S. aureus, a specific variant stream was found to block human complement system; for the horse S. aureus, the specific equine variant of SCIN was indicated to inhibit the horse complement system.

Accordingly, A specific Human monoclonal antibodies (humAbs), named as 6D4, was abstracted from B-cells screened randomly, which specifically binds the SCIN and C3 convertases as inhibitors against S. aureus.

In this article, it is further proposed that compared with S. aureus that evolves across host animal species with closer genetic distances, COVID-19 virus originates from the wild species with longer genetic distance to human, which is evolved into adaptation on human host by acquisition of human gene segments for self-modification of virus genome. This is one of the key factor to explain why COVID-19 is more epidemic than before.

2.The inhibition proteinases over a broader range of biological phyla.
The specificity of host–pathogen interactions in pathogenesis against melanin synthesized by the host cells of invertebrates, which is activated by prophenoloxidase pathway of metabolic process, is discussed . Further more, there are totally six families of serine proteinase inhibitors, including Kazal, Kunitz, α-macroglobulin, Serpin and two recently reported families of low molecule weight , which functions in arthropod hemolymph immunology system to defense against a broad ranges of pathogens or parasites infections. Multiple families of inhibition protein protease are classified into two types according to the different functions played in the binding process: the active site inhibition protease families and a specific family of α2-macroglobulins. The first type of inhibition protein protease directly bind and inactivate the active functional group of the pathogenic protease molecules, whereas the second protein α2-macroglobulins bind protease of invasive pathogens by its specific metabolic process trapping molecules, in which the bound protease are converted into a endocytic system mediated by receptors, and subsequently this causes degradation in secondary lysosomes. The α2-macroglobulins are reported in a wide range of biological Kingdom, which is consequently considered as the expression of conserved chromosome arm in the 0.6 billion evolutionary process.   

In this article, it is further suggested that the functional group triggering the catalytic reaction of the same isozyme family is expressed by the conserved genomes in the evolutionary process, so the above protein protease families summarized also becomes the functional groups of chemical species for Research & Development in isozyme Technology, which can be commonly used in other biological species. In my previous article, the enzyme families of botanical species expressed under environmental stress is summarized in a table as systematic analysis of metabolomics study, which would be the linkage gene traits of host-pathogen interactions. However, this article more specifically targets the inhibition protein against invasive pathogens.      

3.Host-Invasion interactions on plants
The polygalacturonase-inhibiting protein (PGIP) derived from plants was studied on the interaction with endopolygalacturonases abstracted from fungi. PGIP's plays a role in endopolygalacturonases which increase the synthesis of oligogalacturonides in which the active sites act as elicitors of phytoalexin (antibiotic) accumulation. This is important to other plant defense reactions.Specifically when oligogalacturonides reaches polymerization higher than nine degree are capable of eliciting phytoalexin synthesis of soybean cotyledons. In comparison, excessive PGIP was added to the digestion of polygalacturonic acid with the same amount of enzyme, the production rate of elicitor-active oligogalacturonides was significantly altered. 

The xylem sap derived from cotton with infection by V. dahliae were tested by proteomics . In total 1717 proteins species were identified as significant accumulation in ND601 inoculated by V. dahliae, which is resistant to disease, whereas 1476 proteins species were significantly accumulated detected in a susceptible variety of CCRI8 inoculated with V. dahliae. It is drown the conclusion that the species of upregulated-protein were pathogenic protein species or relevant with cell-wall, but the majority of downregulated proteins shows relations to plant growth and development. There are six α‐amylase inhibition types in total were summarized, mainly including lectin, knottin, cerea, Kunitz, γ‐purothionin and thaumatin applied in the control of pest. The active sites of molecular structure in α‐amylase inhibitors show significant differences in the diversity of inhibition modes, including proteinase inhibitory or chitinase activity . Further more, the varieties of α‐amylase inhibitors can be examined by isozyme technology . Additionally, the not-specific gene transcriptional regulation for nitrogen oxide production is point out in many plant defense activities .

In this plant section, I hereby characterize the specificity of enzyme/protease/proteinase on host-pathogen interactions over the whole biological kingdoms: firstly, compared with the not-specific gene expression of physiological defense (such as synthesis of nitrogen oxide production in plant), the specific host enzyme species correspond to the specific variety of pathogens due to the inter-dependent evolution in the long-term between both parties; secondly, this specificity of protease synthesis is sometimes coupled with the inoculation of third party microbes as to trigger the active immunological enzyme production discussed above; thirdly, the dose of enzyme production is specific as well; finally, in comparison to the proteomics test of not-selective proteins which detects and examines a large number of protein species above, the enzyme species test more specifically targets the specific disease infection or pest invasion, which uses the same catalyzing pathway by isozyme technology developed in my study, and consequently understand the pathways of immunological process. Please note: the same isozyme family is not identical to the same enzyme/protease/proteinase family in definitions, and none of them are identical to the protein definition as well.      

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