In nature, a large portion of microorganisms survive in the form of biofilms, making them resistant to the removal of clinical antibiotics and the human immune system. Conventional antibiotics can kill planktonic bacteria and surface bacteria, and clinical symptoms can be alleviated, but the bacteria in the biofilm are difficult to remove. The bacteria remaining in the biofilm will multiply quickly after stopping the drug, making the infection symptoms recur again. The extensive use of antibiotics in the long-term repeated treatment process has led to the continuous generation of drug-resistant strains, which has brought greater problems to treatment. Therefore, the development of new target drugs brings new hope for the treatment of bacterial infections.
Qurum sensing (QS) refers to that bacteria can spontaneously generate and release some specific signal molecules, and can sense their concentration changes to regulate the group behavior of microorganisms. Bacteria sense signal changes, start the expression of bacterial related genes to adapt to environmental changes, and show some unique physiological characteristics, including the production of pathogenic bacteria extracellular enzymes and toxins, biofilm formation, bacterial luminescence, pigment production, etc. Blocking the signal transmission between bacteria can reduce the pathogenicity of bacteria. Compared with traditional antibiotics, QS inhibitors do not have a strong survival pressure on bacteria and avoid the production of drug-resistant strains. Such compounds have great research value.
The research team of Zhang Lixin, the Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, collaborated with Professor Wang Yuqiang of the “Thousand Talents Program†of Jinan University to conduct a Qualcomm Pseudomonas aeruginosa QS inhibitor high-pass on the laboratory ’s natural product library and compound library Through quantitative screening, it was found that andrographolide derivative AL-1 (14-Alpha-lipoyl andrographolide) can effectively inhibit the formation of Pseudomonas aeruginosa biofilm, and at the same time inhibit the synthesis of the toxic factors pyocyanin and extracellular polysaccharides, flagella Mediated swimming and clumpiness, and almost no effect on its growth.
The study found that AL-1 can competitively inhibit the binding of the receptor protein LasR and the signaling molecule 3-o-C12-HSL, inhibit the transcription of Las and Rhl system genes, and affect the biofilm matrix polysaccharide Psl at the transcription and translation levels. Synthesis (illustration). At the same time, when AL-1 is used in combination with the commonly used Pseudomonas aeruginosa antibiotics azithromycin, ciprofloxacin, streptomycin, etc., the use of antibiotics can be reduced, but the formation of P. aeruginosa biofilms can be significantly reduced. And the production of extracellular polysaccharides and pyocyanin.
The research results have been published online in the international pharmaceutical journal Antimicrobial Agents and Chemotherapy one after another, which provides new ideas for the clinical treatment of biofilm-related infections.
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