Combined inhibitory activity of Alginate Oligosaccharide and cephalosporin antibiotics against drug-resistant bacteria

At present, the problem of infection treatment caused by drug-resistant bacteria is becoming more and more serious. Clinically common drug-resistant bacteria include Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Acinetobacter baumannii. The development cost of new antibiotics is high, and the combined effect of existing antibacterial synergists is also declining. The development and application of new anti-infective treatment strategies are becoming increasingly urgent. Alginate is composed of mannuronic acid and guluronic acid connected by 1,4-glycosidic bonds and a few 1,5-glycosidic bonds. Its fragments are similar to bacterial endogenous oligosaccharides and have unique biological activities. It has been reported that guluronic acid oligosaccharides (OligoG) obtained by degrading alginate can be used in combination with different antibiotics to inhibit the growth of a variety of resistant bacteria, and can be used in combination with antifungal agents to inhibit the growth of fungi.

In this study, different degradation conditions were used to degrade sodium alginate, and 4 kinds of oligomeric degradation products (ADP) mainly containing mannuronic acid were obtained, which were combined with 6 kinds of cephalosporin antibiotics. With drug-resistant Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and pan-resistant Acinetobacter baumannii as the test subjects, the antibacterial activity was screened by the 96-well plate doubling dilution method. Calculate the antibacterial rate to evaluate the effect of ADP and cephalosporin antibiotics in inhibiting drug-resistant bacteria.

A: Pseudomonas aeruginosa, B: Staphylococcus aureus, C: Acinetobacter baumannii, D: Escherichia coli, I: Before combination, II: After combination

Experimental results: After the combination of 4 kinds of ADP and cephalosporin antibiotics, the antibacterial rate was mostly increased to more than 80%, especially after the combination of cefradine and ADP-3, the inhibition rate of drug-resistant Pseudomonas aeruginosa increased by 116 times. The results suggest that the oligomeric degradation product of sodium alginate (Alginate Oligosaccharide) can be further developed into an antibacterial and synergistic drug.



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