Application Of Synergetic Set Of TRIZ Priciples For Developing cAMP - Accumulation Activators And Their Influence On Multi-Drug Resistance Microorganisms
Keywords:
cAMP-inducers, antimicrobials, MDR strains, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, bacterial growth, sensitivity to antimicrobials, TRIZ, theory of inventive problem solving, Altshuller, TRIZ in pharmaceutical industry and pharmacology, Laws of technical systems evolAbstract
Introduction. The control over multi-resistant nosocomial strains of microorganisms has been becoming increasingly urgent in recent years. We suggest a new paradigm that is eliminating MDR bacteria death, but makes them sensitive to antibiotics. Based on our paradigm will be decreased and suppressed future selection of resistant bacterial strains. The mechanism of action of the enhancers is caused by the activation of the cAMP high doses accumulation process in the microbial cells. cAMP itself is a substrate for phosphorylation including DNA polymerases. Applying synergetic set of TRIZ Principles from matrix of contradictions, we created pioneer new paradigm to fight multi drug resistant bacteria, which could be not only treated generally, killing “unkillable” bacteria by also it could be done by low dosage antibiotics, which is extremely important for treating patients. Materials and methods. MDR resistant strains Pseudomonas aeruginosa MDR Kharkov IMI1, Acinetobacter baumannii MDR Kharkov-IMI1, and Klebsiella pneumoniae MDR Kharkov-IMI1 were used. The following antimicrobial agents of known potency were evaluated: ciprofloxacin, polymyxin B, and amikacin. Characteristics of bacterial growth were determined in a nutrient medium compared to the control group – the broth without the enhancers. cAMP-inducers (Enhancers) are the derivatives of bis-pyrimidine, isoquinoline and benzimidazole from superfamily phosphodiesterase inhibitors. Results and discussion. Enhancers contribute to a significant increase in the antimicrobial sensitivity to polymyxin, ciprofloxacin and amikacin in multi-resistant strains of bacteria. During our research process changes in the growth characteristics and antimicrobial sensitivity are observed mainly in the second passage that demonstrates the need for further studies of the molecular mechanisms of the cAMP effect on the division and growth of microbial cell –based on our TRIZ approach we may find solution to resolve MDR resistance in infectious disease for different types of MDR microorganisms.
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