Artificial combined antibacterial engineering polypeptide and its preparation method

Abstract

The present invention discloses an artifically-combined antimicrobial engineering polypeptide. Said polypeptide is formed from pathogen signal transducing polypeptide and colicine capable of forming ion channel or its water porous channel structural domain. Its molecular structure is connection of carboxyl terminal of colicine or its water porous channel structural domain and amino terminal of signal transducing polypeptide or connection of its amino terminal and carboxyl terminal of signal trasducing polypeptide. molecular weight of the polypeptide is 10000-63000, it can be respectively connected with signal transducing polypeptide of different pathogen, and can form the engineering polypeptide resisting said pathogen. Said invented polypeptide preparation method utilizes the point mulation technique to insert the pathogen signal transducing polypeptide gene into the site selected by colicine gene loaded in the engineering plasmid, then transports the mutation plasmid into engineering bacterium to make production. It does not make bacteria produce resistance to drug, and can change signal tranducing polypeptide to produce any antibiotic.

Description

1. Technical field [0001] The invention relates to an artificially combined antibacterial engineering polypeptide and a preparation method thereof. The antibacterial purpose is achieved by preparing the engineered polypeptide (Engineered peptide) composed of different bacterial toxins and functional domains of signal transduction polypeptides. 2. Background technology [0002] Bacterial infection is still a major threat to human life and health. Since the advent of sulfonamides and penicillins, antibiotics have been invented by humans to achieve antibacterial effects by inhibiting bacterial cell wall synthesis, inhibiting or interfering with bacterial nucleic acid and protein metabolism and synthesis. However, these antibacterial pathways can easily induce bacteria to mutate and produce antimicrobial resistance. Therefore, people have been devoting themselves to the development of new antibiotics. The direct formation of ion channels on the bacterial cell membrane to cause ...

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Problems solved by technology

However, the research in this direction has been progressing slowly. For example, the signal transduction polypeptide of Staphylococcus aureus, Agr D, was finally found out to be an octapeptide until 1995 (Ji et al, Cell density control of staphylococcal virus mediated by an octapeptide pheromone. Proc Natl Acad Sci USA.92: 12055-12059 (1995)), found in 1999 that adding this synthetic octapeptide in the early or middle and late logarithmic phase of Staphylococcus aureus can stimulate or inhibit the growth of Staphylococcus aureus. Growth (Mayville et al, Structure-activity analysis of synthetic autoinducing thiolactone peptides from staphylococcus aureus responsible for virus. Proc Natl Acad Sci USA. 96: 1218-1223 (1999))

[0004] As mentioned above, colistin is an ideal ion channel antibiotic, but its disadvantage is that it can only act on Gram-negative bacilli such as Escherichia coli

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