Drug control of biofilm dispersion due to regulation of the activity of bacterial cyclic guanosine monophosphate (part 2)
Keywords:bacterial biofilms, dispersion, c-di-GMP, antibiofilm therapy
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.
Abaturov AE, Kryuchko TA. Dispersion of bacterial biofilm and chronization of respiratory tract infection. Zdorov`e rebenka. 2019;14(5):337-342. doi: 10.22141/2224-05188.8.131.529.177411. (in Russian).
Abaturov AE, Yulish EI. The role of interferons in the protection of the respiratory tract, part 1: Cascade of excitation of the system of interferons. Zdorov`e rebenka. 2007;(5):136-144. (in Russian).
Ahonen MJR, Dorrier JM, Schoenfisch MH. Antibiofilm Efficacy of Nitric Oxide-Releasing Alginates against Cystic Fibrosis Bacterial Pathogens. ACS Infect Dis. 2019;5(8):1327–1335. doi: 10.1021/acsinfecdis.9b00016.
Allan RN, Kelso MJ, Rineh A, et al. Cephalosporin-NO-donor prodrug PYRRO-C3D shows β-lactam-mediated activity against Streptococcus pneumoniae biofilms. Nitric Oxide. 2017;65:43–49. doi: 10.1016/j.niox.2017.02.006.
Antoniani D, Bocci P, Maciag A, Raffaelli N, Landini P. Monitoring of diguanylate cyclase activity and of cyclic-di-GMP biosynthesis by whole-cell assays suitable for high-throughput screening of biofilm inhibitors. Appl Microbiol Biotechnol. 2010;85(4):1095–1104. doi: 10.1007/s00253-009-2199-x.
Antoniani D, Rossi E, Rinaldo S, et al. The immunosuppressive drug azathioprine inhibits biosynthesis of the bacterial signal molecule cyclic-di-GMP by interfering with intracellular nucleotide pool availability. Appl Microbiol Biotechnol. 2013;97(16):7325–7336. doi: 10.1007/s00253-013-4875-0.
Barraud N, Kardak BG, Yepuri NR, et al. Cephalosporin-3'-diazeniumdiolates: targeted NO-donor prodrugs for dispersing bacterial biofilms. Angew Chem Int Ed Engl. 2012;51(36):9057–9060. doi: 10.1002/anie.201202414.
Collins SA, Kelso MJ, Rineh A, et al. Cephalosporin-3'-Diazeniumdiolate NO Donor Prodrug PYRRO-C3D Enhances Azithromycin Susceptibility of Nontypeable Haemophilus influenzae Biofilms. Antimicrob Agents Chemother. 2017;61(2):e02086-16. doi: 10.1128/AAC.02086-16.
de la Fuente-Núñez C, Reffuveille F, Fairfull-Smith KE, Hancock RE. Effect of nitroxides on swarming motility and biofilm formation, multicellular behaviors in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2013;57(10):4877–4881. doi: 10.1128/AAC.01381-13.
Fernicola S, Paiardini A, Giardina G, et al. In Silico Discovery and In Vitro Validation of Catechol-Containing Sulfonohydrazide Compounds as Potent Inhibitors of the Diguanylate Cyclase PleD. J Bacteriol. 2015;198(1):147–156. doi: 10.1128/JB.00742-15.
Fernicola S, Torquati I, Paiardini A, et al. Synthesis of Triazole-Linked Analogues of c-di-GMP and Their Interactions with Diguanylate Cyclase. J Med Chem. 2015;58(20):8269–8284. doi: 10.1021/acs.jmedchem.5b01184.
Hasan N, Cao J, Lee J, et al. PEI/NONOates-doped PLGA nanoparticles for eradicating methicillin-resistant Staphylococcus aureus biofilm in diabetic wounds via binding to the biofilm matrix. Mater Sci Eng C Mater Biol Appl. 2019;103:109741. doi: 10.1016/j.msec.2019.109741.
Kalia D, Merey G, Nakayama S, et al. Nucleotide, c-di-GMP, c-di-AMP, cGMP, cAMP, (p)ppGpp signaling in bacteria and implications in pathogenesis. Chem Soc Rev. 2013;42(1):305–341. doi:10.1039/c2cs35206k.
Kang D, Kirienko NV. High-Throughput Genetic Screen Reveals that Early Attachment and Biofilm Formation Are Necessary for Full Pyoverdine Production by Pseudomonas aeruginosa. Front Microbiol. 2017;8:1707. doi:10.3389/fmicb.2017.01707.
Koo H, Allan RN, Howlin RP, Stoodley P, Hall-Stoodley L. Targeting microbial biofilms: current and prospective therapeutic strategies. Nat Rev Microbiol. 2017;15(12):740–755. doi:10.1038/nrmicro.2017.99.
Lieberman OJ, Orr MW, Wang Y, Lee VT. High-throughput screening using the differential radial capillary action of ligand assay identifies ebselen as an inhibitor of diguanylate cyclases. ACS Chem Biol. 2014;9(1):183–192. doi:10.1021/cb400485k.
Matsuyama BY, Krasteva PV, Baraquet C, Harwood CS, Sondermann H, Navarro MV. Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2016;113(2):E209–E218. doi:10.1073/pnas.1523148113.
McCarthy RR, Valentini M, Filloux A. Contribution of Cyclic di-GMP in the Control of Type III and Type VI Secretion in Pseudomonas aeruginosa. Methods Mol Biol. 2017;1657:213–224. doi:10.1007/978-1-4939-7240-1_17.
Moradali MF, Ghods S, Rehm BHA. Activation Mechanism and Cellular Localization of Membrane-Anchored Alginate Polymerase in Pseudomonas aeruginosa. Appl Environ Microbiol. 2017;83(9):e03499-16. doi:10.1128/AEM.03499-16.
O'Connor JR, Kuwada NJ, Huangyutitham V, Wiggins PA, Harwood CS. Surface sensing and lateral subcellular localization of WspA, the receptor in a chemosensory-like system leading to c-di-GMP production. Mol Microbiol. 2012;86(3):720–729. doi:10.1111/mmi.12013.
Qvortrup K, Hultqvist LD, Nilsson M, et al. Small Molecule Anti-biofilm Agents Developed on the Basis of Mechanistic Understanding of Biofilm Formation. Front Chem. 2019;7:742. doi:10.3389/fchem.2019.00742.
Ravichandran A, Ramachandran M, Suriyanarayanan T, Wong CC, Swarup S. Global Regulator MorA Affects Virulence-Associated Protease Secretion in Pseudomonas aeruginosa PAO1. PLoS One. 2015;10(4):e0123805. doi:10.1371/journal.pone.0123805.
Sambanthamoorthy K, Luo C, Pattabiraman N, et al. Identification of small molecules inhibiting diguanylate cyclases to control bacterial biofilm development. Biofouling. 2014;30(1):17–28. doi:10.1080/08927014.2013.832224.
Sambanthamoorthy K, Sloup RE, Parashar V, et al. Identification of small molecules that antagonize diguanylate cyclase enzymes to inhibit biofilm formation. Antimicrob Agents Chemother. 2012;56(10):5202–5211. doi:10.1128/AAC.01396-12.
Skariyachan S, Sridhar VS, Packirisamy S, Kumargowda ST, Challapilli SB. Recent perspectives on the molecular basis of biofilm formation by Pseudomonas aeruginosa and approaches for treatment and biofilm dispersal. Folia Microbiol (Praha). 2018;63(4):413–432. doi:10.1007/s12223-018-0585-4.
Soren O, Rineh A, Silva DG, et al. Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa. J Antimicrob Chemother. 2020;75(1):117–125. doi:10.1093/jac/dkz378.
Wang J, Zhou J, Donaldson GP, et al. Conservative change to the phosphate moiety of cyclic diguanylic monophosphate remarkably affects its polymorphism and ability to bind DGC, PDE, and PilZ proteins. J Am Chem Soc. 2011;133(24):9320–9330. doi:10.1021/ja1112029.
Wei Q, Leclercq S, Bhasme P, et al. Diguanylate Cyclases and Phosphodiesterases Required for Basal-Level c-di-GMP in Pseudomonas aeruginosa as Revealed by Systematic Phylogenetic and Transcriptomic Analyses. Appl Environ Microbiol. 2019;85(21):e01194-19. doi:10.1128/AEM.01194-19.
Wo Y, Li Z, Brisbois EJ, et al. Origin of Long-Term Storage Stability and Nitric Oxide Release Behavior of CarboSil Polymer Doped with S-Nitroso-N-acetyl-D-penicillamine. ACS Appl Mater Interfaces. 2015;7(40):22218–22227. doi:10.1021/acsami.5b07501.
Zheng Y, Tsuji G, Opoku-Temeng C, Sintim HO. Inhibition of P. aeruginosa c-di-GMP phosphodiesterase RocR and swarming motility by a benzoisothiazolinone derivative. Chem Sci. 2016;7(9):6238–6244. doi:10.1039/c6sc02103d.
Zhou E, Seminara AB, Kim SK, Hall CL, Wang Y, Lee VT. Thiol-benzo-triazolo-quinazolinone Inhibits Alg44 Binding to c-di-GMP and Reduces Alginate Production by Pseudomonas aeruginosa. ACS Chem Biol. 2017;12(12):3076–3085. doi:10.1021/acschembio.7b00826.
Copyright (c) 2020 А.Е. Abaturov
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our edition uses the copyright terms of Creative Commons for open access journals.
Authors, who are published in this journal, agree with the following terms:
- The authors retain rights for authorship of their article and grant to the edition the right of first publication of the article on a Creative Commons Attribution 4.0 International License, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.
- Directing the article for the publication to the editorial board (publisher), the author agrees with transmitting of rights for the protection and using the article, including parts of the article, which are protected by the copyrights, such as the author’s photo, pictures, charts, tables, etc., including the reproduction in the media and the Internet; for distributing; for the translation of the manuscript in all languages; for export and import of the publications copies of the writers’ article to spread, bringing to the general information.
- The rights mentioned above authors transfer to the edition (publisher) for the unlimited period of validity and on the territory of all countries of the world.
- The authors guarantee that they have exclusive rights for using of the article, which they have sent to the edition (publisher). The edition (the publisher) is not responsible for the violation of given guarantees by the authors to the third parties.
- The authors have the right to conclude separate supplement agreements that relate to non-exclusive distribution of their article in the form in which it had been published in the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.
- The policy of the journal permits and encourages the publication of the article in the Internet (in institutional repository or on a personal website) by the authors, because it contributes to productive scientific discussion and a positive effect on efficiency and dynamics of the citation of the article.
- The rights to the article are deemed transferred by the authors to the edition (the publisher) since the moment of the publication of the article in the printed or electronic version of journal.