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The extracellular matrix of biofilms ensures the fixation of the biofilm on the biological surface and the protection of its bacteria from external adverse factors. The main structural component of biofilms is an extracellular polysaccharide substance. Exopolysaccharides and amyloid-like fibers are considered key molecular structures that support the three-dimensional structure of biofilms. Until recently, it was assumed that most biofilm dispersion mechanisms are associated with the functioning of matrix degrading enzymes, such as glycoside hydrolases, polysaccharide lyases, and proteases. However, it has been demonstrated that small molecules play an independent role in the process of destruction of matrix exopolysaccharides and amyloid-like fibers. Among the compounds that violate the biofilm matrix, anti-matrix molecules, compounds interacting with microdomains of the bacterial membrane and bacterial surfactants (biosurfactants) are distinguished. It has been demonstrated that compounds of these groups can inhibit the formation of biofilms and contribute to the dispersion of biofilms. From the group of anti-matrix molecules, the polyamine compound norspermidine interacts with exopolysaccharides, and the derivatives of benzoquinone AA-861 and sesquiterpene lactone parthenolide interact with TasA-amyloid-like fibers. Norspermidine prevents the formation and dispersion of biofilms of various bacteria, including Acinetobacter baumannii, Bacillus subtili, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphy­lococcus aureus, Staphylococcus epidermidis. Compound AA-861 is active against biofilms, which are formed by the bacteria Streptococcus mutans, Bacillus cereus, Escherichia coli. Parthenolide disperses biofilms formed by Escherichia coli and Bacillus cereus. Zaragozic acid, interacting with microdomains of the bacterial membrane, disruptі the functioning of raft-associated bacterial proteins. Small anti-matrix molecules and bacterial membranes aimed at microdomains that initiate biofilm dispersion will certainly become the basis for the development of effective antibiofilm therapeutic drugs.

Mucolytic drugs have the ability to disrupt the structure of the matrix and destroy the formed bacterial biofilms. The most studied is N-acetylcysteine. Ciro Pérez-Giraldo et al. first demonstrated the antibiofilm activity of N-acetylcysteine in 1997, which showed that it has an inhibitory effect on bacterial growth and induces the dispersion of biofilms formed by bacteria Staphylococcus epidermidis. N-acetylcysteine has been established to have a pronounced activity against biofilms formed by various gram-positive and gram-negative bacteria, including antibiotic-resistant bacterial strains of methicillin-resistant Staphylococcus aureus and quinolone-resistant Pseudomonas aeruginosa. N-acetylcysteine promotes penetration of penicillins, polymyxins, fluoroquinolones into the deepest layers of the biofilm, overcoming the antibiotic resistance of causative bacterial agents. N-acetylcysteine can be used as an antibiotic drug for chronic bacterial-associated diseases, in particular, episodes of respiratory infections in patients with cystic fibrosis, chronic bronchitis, and chronic obstructive pulmonary disease. N-acetylcysteine is believed to be a drug with an excellent safety and efficacy profile in the treatment of diseases that are accompanied by the formation of bacterial biofilms. N-acetylcysteine and nanotechnological drugs, in which its molecules are combined with gallium or silver particles, are medicines that can become the drugs of choice that disperse biofilms and enhance the effectiveness of antibiotic therapy, especially for diseases caused by antibiotic-resistant strains of microorganisms.

Extracellular bacterial DNA (eDNA) is actively involved in the formation and vital activity of biofilms, acting as a major structural component of the matrix. The release of eDNA into the biofilm continuum is due to bacterial cell lysis and active secretion by a lysis-independent mechanism. Molecules of eDNA are present in species-specific amounts in biofilms of different microorganisms and are organized as clear morphological formations forming mesh structures or filamentous networks. The importance of eDNA in maintaining matrix stability is particularly high in the early stages of biofilm development. EDNA is involved in biofilms: as a factor contributing to bacterial adhesion, biofilm formation, and extracellular matrix production; as a structural component in ensuring matrix stability; as a substrate for the process of gene transfer through transformation of competent sister bacteria; as a nutrient and as a protective factor of bacterial biofilms. Reducing the content of eDNA destabilizes the matrix, which promotes the release of bacteria from biofilms and, as a consequence, increases the sensitivity of pathogens to the action of antibacterial agents. Clea­vage of eDNA molecules by DNase is one of the ways of degradation of the biofilm matrix and overcoming bacterial antibiotic resistance associated with biofilm formation. It has been shown that DNases, in particular DNase I, DNase 1L2, NucB nuclease, effectively destroy young biofilms of different Gram-negative and Gram-positive bacteria. Currently, DNases are considered as possible models of future antibiofilm drugs. Given the lack of long-term activity and the limited depth of penetration in the dispersion of biofilms of these drugs, a nanotechnological DNA mimetic artificial enzyme was developed and synthesized, which has a high level of DNase-like antibiofilm activity. In the clinical practice, highly purified human recombinant DNase I — dornase alpha — is being successfully used in the treatment of infections in patients with cystic fibrosis.

Развитие бактериальных биопленок зависит от секреции и сохранения внеклеточных полисахаридов, или экзополисахаридов, которые являются основными компонентами внеклеточного полисахаридного вещества биопленок. Экзополисахариды внеклеточного полисахаридного вещества обеспечивают структурную стабильность биопленки, адгезию и агрегацию микроорганизмов, физическую и химическую защиту бактерий от действия противомикробных препаратов и эффекторов иммунной системы макроорганизма. Бактериальные клетки, расположенные в биопленке, защищены от антибактериальных эндо- и экзофакторов внеклеточным полимерным матриксом. Для инициирования диспергирования биопленок микроорганизмы наряду с другими ферментами используют специфические гликозидгидролазы, которые разрушают полисахариды бактериальных биопленок. Гликозидгидролазы реализуют свое действие через гидролиз гликозидных связей: амилазы расщепляют α-1,4-; целлюлазы — β-1,4-; β-галактозидазы — β-1,3-гликозидные связи. Основными гликозидгидролазами, которые обладают антибиопленочным действием, являются: α-лизоцим, амилазы, дисперсин B, целлюлазы, гиалуронидаза, α- и β-маннозидазы, альгинат-лиазы. Данные ферменты вызывают разрушение полисахаридных полимеров, способствуя высвобождению бактерий. Бактерии, которые лишились защиты полисахаридного каркаса, подвергаются воздействию антибактериальных агентов. С учетом того, что деградация экзополисахаридов биопленок гликозидгидролазами приводит к выраженному диспергированию бактерий, данный антибиопленочный метод лечения может представлять собой универсальный подход к терапии инфекций, протекающих с формированием биопленок. Медикаментозные методы диспергирования биопленок при помощи полисахаридразрушающих ферментов, без сомнения, расширят арсенал антибиопленочной терапии хронических и рецидивирующих бактериальных инфекций, особенно вызванных антибиотикорезистентными бактериями.

Biofilms protect bacteria from the action of antibacterial drugs and are one of the mechanisms of antibiotic resistance of infections. Destruction of the bacterial biofilm matrix leads to the release of bacteria and they again become vulnerable to antibacterial agents. Various enzymes are involved in the degradation of various components of the excellular matrix of biofilms: proteases, glycosidases, deoxyribonucleases, which are secreted by bacteria and macroorganism cells. Numerous bacterial proteases and proteases of animal origin contribute to the dispersion of biofilms. Proteases are divided into two main groups: exo- and endopeptidases. Exopeptidases are involved in the dispersion of biofilms. Bacterial proteases perform two main functions: firstly, they are involved in providing the microorganism with peptide nutrients and, secondly, they contribute to the development of the infectious process. Bacteria of each family produce several proteases, the activity of which is directed against various targeted molecules. Bacterial proteases such as aureolysin, staphopaines A and B, streptococcal cysteine protease, V8 serine protease, Spl protease, lysostaphin, LasВ protease, LapG protease, serratiopeptidase, proteinase K, subtilisin and subtilisin-like enzymes that are involved in the breakdown of the bioprotein matrix contribute to the release of pathogenic bacteria, which leads to an increase in the effectiveness of antibiotic therapy and reduces the risk of an adverse course of severe bacterial infections. It has now been shown that the use of recombinant forms of lysostaphin, serratiopeptidase, proteinase K is accompanied by a decrease in the weight of the biofilm or its complete degradation and contributes to the sanogenesis of infectious diseases. Despite the fact that most of the identified proteases with antibiotic activity are currently in the phase of experimental study, there is no doubt that drugs developed on their basis will become drugs that will be used in the treatment of diseases caused by antibiotic-resistant infections.

The infectious process caused by pathogenic bacteria can be accompanied by the formation of a biofilm, which determines the safety of bacteria and a decrease in the effectiveness of antibacterial agents. The development of drugs that contribute to the dispersion of bacterial biofilms is one of the most important therapeutic areas that contribute to solving the problem of treating bacterial infections caused by microorganisms that are resistant to antibacterial agents. One of the target bacterial molecules involved in biofilm formation, which can be subjected to drug regulation, is a secondary messenger nucleoside molecule — cyclic dinucleotide GMP (c-di-GMP). Drug suppression of the level of intra-bacterial concentration of the messenger molecule of c-di-GMP or blocking its activity helps prevent the formation and causes the destruction of the bacterial biofilm, which is accompanied by an increase in the level of effectiveness of treatment of bacterial infections. A decrease in the level of intra-bacterial concentration of c-di-GMP can be achieved by inhibiting the synthesis processes due to: 1) suppression of diguanylate cyclase activity; 2) restrictions on the availability of substrates required for the synthesis of c-di-GMP; 3) increased degradation of the c-di-GMP molecule due to activation of phosphodiesterase activity. The treatment of infectious diseases, which are accompanied by the formation of biofilms, requires the medical induction of the dispersion of bacteria from biofilms and the use of targeted antibiotic drugs that cause the death of bacteria released from biofilms. The use of analogues of c-di-GMP, which disrupt the functioning of native c-di-GMP, and the blocking of targeted receptors and other molecular structures can also lead to dispersion of the bacterial biofilm. Medicines that modulate the activity of ­c-di-GMP will increase the effectiveness of the treatment of bacterial infections, which are accompanied by the formation of biofilms.

The infectious process caused by pathogenic bacteria can be accompanied by the formation of a biofilm, which determines the safety of bacteria and a decrease in the effectiveness of antibacterial agents. The development of drugs that contribute to the dispersion of bacterial biofilms is one of the most important therapeutic areas, which help solve the problem of treating bacterial infections caused by microorganisms that are resistant to antibacterial agents. One of the target bacterial molecules involved in biofilm formation, which can be subjected to drug regulation, is a nucleotide secondary messenger molecule — cyclic dinucleotide guanosine monophosphate (c-di-GMP). Drug suppression of the level of intra-bacterial concentration of the messenger molecule of c-di-GMP or blocking its activity helps prevent the formation of bacterial biofilm and leads to its destruction, which is accompanied by an increase in the level of effectiveness of treatment of bacterial infections. A decrease in the level of intra-bacterial concentration of c-di-GMP can be achieved by inhibiting the synthesis processes due to: 1) suppression of diguanylate cyclase activity; 2) restriction on the availability of substrates required for the synthesis of c-di-GMP; 3) increased degradation of c-di-GMP molecule due to activation of phosphodiesterase activity. The treatment of infectious diseases, which are accompanied by the formation of biofilms, requires the medical induction of the dispersion of bacteria from biofilms and the use of targeted antibiotic drugs that cause the death of bacteria released from biofilms. The use of c-di-GMP analogues, which disrupt the functioning of native c-di-GMP, and the blocking of targeted receptors and other molecular structures can also lead to the dispersion of bacterial biofilm. Medicines that modulate the activity of c-di-GMP will increase the effectiveness of the antibacterial treatment of bacterial infections, which are accompanied by the formation of biofilms.

In a colonized environment, pathogenic bacteria change the form of existence from the planktonic to the microbiosocial, forming a peculiar structure, the so-called biofilm. The formation of biofilm is a key factor in the virulence of a wide range of pathogenic bacteria that cause both acute and chronic infections. The tolerance of biofilm bacteria to antibacterial agents underlies the majority of recurrent and chronic infectious diseases. Currently, therapeutic strategies are being developed to solve this problem. These strategies are aimed at suppressing the vital activity of biofilms. The therapeutic agents for protection against pathogenic bacterial biofilms are divided into two large groups. The first group are compounds that inhibit the formation of biofilms, and the second group are compounds that destabilize or destroy the structure of a mature formed biofilm. There is experimental evidence that the use of these drugs will be effective in the treatment of diseases associated with the formation of biofilms.

Copyright of Zdorov'ye Rebenka is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Urinary tract infection (UTI) in children is a topical issue not only for nephrologists, but also for pediatricians. Success in the treatment depends on timely diagnosis of UTI and adequate antibiotic therapy. The work presents features of pathogens, such as the formation of beta-lactamases and the formation of bacterial biofilms, which at the present stage impede the diagnosis and lead to antibiotic resistance. Based on literature data and own observations, the use of Sulbactomax, a third-generation cephalosporin, in children with UTI has been substantiated.

Copyright of Zdorov'ye Rebenka is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zdorov'ye Rebenka is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)