Polysaccharide-degrading enzymes as agents dispersing bacterial biofilms

А.Е. Abaturov


The development of bacterial biofilms depends on the secretion and preservation of extracellular polysaccharides, or exopolysaccharides, which are the main components of the extracellular polysaccharide substance of the biofilms. Exopolysaccharides of the extracellular polysaccharide substance provide the structural stability of the biofilm, the adhesion and aggregation of microorganisms, the physical and chemical protection of bacteria from the action of antimicrobials and immune system effectors of the macroorganism. Bacterial cells located in the biofilm are protected from antibacterial endo- and exofactors by an extracellular polymeric matrix. To initiate the dispersion of biofilms, microorganisms, along with other enzymes, use specific glycoside hydrolases, which destroy polysaccharides of bacterial biofilms. Glycoside hydrolases realize their action through the hydrolysis of glycosidic bonds: amylases cleave α-1,4-; cellulases — ­β-1,4-; β-galactosidases — β-1,3-glycosidic bonds. The main glycoside hydrolases that have antibiotic action are: α-lysozyme, amylases, dispersin B, cellulases, hyaluronidase, α- and β-mannosidases, alginate lyases. These enzymes cause the destruction of polysaccharide polymers, contributing to the release of bacteria. Bacteria that have lost the protection of the polysaccharide scaffold are exposed to antibacterial agents. Considering that the degradation of exopolysaccharides of biofilms by glycoside hydrolases leads to pronounced dispersion of bacteria, this antibiofilm treatment method can be a universal approach to the treatment of infections occurring with the formation of biofilms. Drug methods of dispersing biofilms using polysaccharide-degrading enzymes will no doubt expand the arsenal of antibiofilm therapy for chronic and recurrent bacterial infections, especially those caused by antibio­tic-resistant bacteria.


bacterial biofilms; dispersion; polysaccharide-degrading enzymes


Alkawash MA, Soothill JS, Schiller NL. Alginate lyase enhances antibiotic killing of mucoid Pseudomonas aeruginosa in biofilms. APMIS. 2006;114(2):131-138. doi:10.1111/j.1600-0463.2006.apm_356.x.

Arnal G, Stogios PJ, Asohan J, et al. Substrate specificity, regiospecificity, and processivity in glycoside hydrolase family 74. J Biol Chem. 2019;294(36):13233-13247. doi:10.1074/jbc.RA119.009861.

Baroroh U, Yusuf M, Rachman SD, et al. The Importance of Surface-Binding Site towards Starch-Adsorptivity Level in α-Amylase: A Review on Structural Point of View. Enzyme Res. 2017;2017:4086845. doi:10.1155/2017/4086845.

Berlemont R, Martiny AC. Phylogenetic distribution of potential cellulases in bacteria. Appl Environ Microbiol. 2013;79(5):1545-1554. doi:10.1128/AEM.03305-12.

Chaignon P, Sadovskaya I, Ragunah Ch, Ramasubbu N, Kaplan JB, Jabbouri S. Susceptibility of staphylococcal biofilms to enzymatic treatments depends on their chemical composition. Appl Microbiol Biotechnol. 2007;75(1):125-132. doi:10.1007/s00253-006-0790-y.

Chen KJ, Lee CK. Twofold enhanced dispersin B activity by N-terminal fusion to silver-binding peptide for biofilm eradication. Int J Biol Macromol. 2018;118(Pt A):419-426. doi:10.1016/j.ijbiomac.2018.06.066.

Cockburn D, Wilkens C, Ruzanski C, et al. Analysis of surface binding sites (SBSs) in carbohydrate active enzymes with focus on glycoside hydrolase families 13 and 77 — a mini-review. Biologia. 2014;69(6):705-712. doi:10.2478/s11756-014-0373-9.

Craigen B, Dashiff A, Kadouri DE. The Use of Commercially Available Alpha-Amylase Compounds to Inhibit and Remove Staphylococcus aureus Biofilms. Open Microbiol J. 2011;5:21-31. doi:10.2174/1874285801105010021.

Ertesvåg H. Alginate-modifying enzymes: biological roles and biotechnological uses. Front Microbiol. 2015;6:523. doi:10.3389/fmicb.2015.00523.

Fekete A, Borbás A, Gyémánt G, et al. Synthesis of β-(1→6)-linked N-acetyl-D-glucosamine oligosaccharide substrates and their hydrolysis by Dispersin B. Carbohydr Res. 2011;346(12):1445-1453. doi:10.1016/j.carres.2011.03.029.

Fleming D, Chahin L, Rumbaugh K. Glycoside Hydrolases Degrade Polymicrobial Bacterial Biofilms in Wounds. Antimicrob Agents Chemother. 2017;61(2):e01998-16. doi:10.1128/AAC.01998-16.

Fleming D, Rumbaugh KP. Approaches to Dispersing Medical Biofilms. Microorganisms. 2017;5(2):15. doi:10.3390/microorganisms5020015.

Ghadam P, Akhlaghi F, Ali AA. One-step purification and characterization of alginate lyase from a clinical Pseudomonas aeruginosa with destructive activity on bacterial biofilm. Iran J Basic Med Sci. 2017;20(5):467-473. doi:10.22038/IJBMS.2017.8668.

Greene ER, Himmel ME, Beckham GT, Tan Z. Glycosylation of Cellulases: Engineering Better Enzymes for Biofuels. Adv Carbohydr Chem Biochem. 2015;72:63-112. doi:10.1016/bs.accb.2015.08.001.

Hogan S, Zapotoczna M, Stevens NT, Humphreys H, O'Gara JP, O'Neill E. Potential use of targeted enzymatic agents in the treatment of Staphylococcus aureus biofilm-related infections. J Hosp Infect. 2017;96(2):177-182. doi:10.1016/j.jhin.2017.02.008.

Janeček Š, Gabriško M. Remarkable evolutionary relatedness among the enzymes and proteins from the α-amylase family. Cell Mol Life Sci. 2016;73(14):2707-2725. doi:10.1007/s00018-016-2246-6.

Kalpana BJ, Aarthy S, Pandian SK. Antibiofilm activity of α-amylase from Bacillus subtilis S8-18 against biofilm forming human bacterial pathogens. Appl Biochem Biotechnol. 2012;167(6):1778-1794. doi:10.1007/s12010-011-9526-2.

Kerrigan JE, Ragunath C, Kandra L, et al. Modeling and biochemical analysis of the activity of antibiofilm agent Dispersin B. Acta Biol Hung. 2008;59(4):439-451. doi:10.1556/ABiol.59.2008.4.5.

Kurasin M, Väljamäe P. Processivity of cellobiohydrolases is limited by the substrate. J Biol Chem. 2011;286(1):169-177. doi:10.1074/jbc.M110.161059.

Lamppa JW, Ackerman ME, Lai JI, Scanlon TC, Griswold KE. Genetically engineered alginate lyase-PEG conjugates exhibit enhanced catalytic function and reduced immunoreactivity. PLoS One. 2011;6(2):e17042. doi:10.1371/journal.pone.0017042.

Lombard V, Bernard T, Rancurel C, Brumer H, Coutinho PM, Henrissat B. A hierarchical classification of polysaccharide lyases for glycogenomics. Biochem J. 2010;432(3):437-444. doi:10.1042/BJ20101185.

Ma L, Conover M, Lu H, Parsek MR, Bayles K, Wozniak DJ. Assembly and development of the Pseudomonas aeruginosa biofilm matrix. PLoS Pathog. 2009;5(3):e1000354. doi:10.1371/journal.ppat.1000354.

Pozzi C, Waters EM, Rudkin JK, et al. Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections. PLoS Pathog. 2012;8(4):e1002626. doi:10.1371/journal.ppat.1002626.

Ragunath C, DiFranco K, Shanmugam M, et al. Surface display of Aggregatibacter actinomycetemcomitans autotransporter Aae and dispersin B hybrid act as antibiofilm agents. Mol Oral Microbiol. 2016;31(4):329-339. doi:10.1111/omi.12126.

Ramasubbu N, Thomas LM, Ragunath C, Kaplan JB. Structural analysis of dispersin B, a biofilm-releasing glycoside hydrolase from the periodontopathogen Actinobacillus actinomycetemcomitans. J Mol Biol. 2005;349(3):475-486. doi:10.1016/j.jmb.2005.03.082.

Saxena P, Joshi Y, Rawat K, Bisht R. Biofilms: Architecture, Resistance, Quorum Sensing and Control Mechanisms. Indian J Microbiol. 2019;59(1):3-12. doi:10.1007/s12088-018-0757-6.

Sukharnikov LO, Cantwell BJ, Podar M, Zhulin IB. Cellulases: ambiguous nonhomologous enzymes in a genomic perspective. Trends Biotechnol. 2011;29(10):473-479. doi:10.1016/j.tibtech.2011.04.008.

Thallinger B, Prasetyo EN, Nyanhongo GS, Guebitz GM. Antimicrobial enzymes: an emerging strategy to fight microbes and microbial biofilms. Biotechnol J. 2013;8(1):97-109. doi:10.1002/biot.201200313.

van Dijl JM, Hecker M. Bacillus subtilis: from soil bacterium to super-secreting cell factory. Microb Cell Fact. 2013;12:3. doi:10.1186/1475-2859-12-3.

Waryah CB, Wells K, Ulluwishewa D, et al. In Vitro Antimicrobial Efficacy of Tobramycin Against Staphylococcus aureus Biofilms in Combination With or Without DNase I and/or Dispersin B: A Preliminary Investigation. Microb Drug Resist. 2017;23(3):384-390. doi:10.1089/mdr.2016.0100.

Watters CM, Burton T, Kirui DK, Millenbaugh NJ. Enzymatic degradation of in vitro Staphylococcus aureus biofilms supplemented with human plasma. Infect Drug Resist. 2016;9:71-78. doi:10.2147/IDR.S103101.

Xu F, Wang P, Zhang YZ, Chen XL. Diversity of Three-Dimensional Structures and Catalytic Mechanisms of Alginate Lyases. Appl Environ Microbiol. 2018;84(3):e02040-17. doi:10.1128/AEM.02040-17.

Yan S, Wu G. Bottleneck in secretion of α-amylase in Bacillus subtilis. Microb Cell Fact. 2017;16(1):124. doi:10.1186/s12934-017-0738-1.

Zhu B, Yin H. Alginate lyase: Review of major sources and classification, properties, structure-function analysis and applications. Bioengineered. 2015;6(3):125-131. doi:10.1080/21655979.2015.1030543.

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