Pharmacological effect on biofilm dispersion. Derivatives of the diffusible signal factor family




dispersion of biofilm, respiratory tract, family of the diffusing signaling factor, recurrent and chronic infectious and inflammatory diseases, review


The scientific review deals with the role of representatives of the family of the diffusible signal factor (DSF), which are cis-2-decenoic acid, in the process of dispersing biofilms of pathogenic bacteria. For writing the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scho­lar, EMBASE, Global Health, The Cochrane Library, CyberLe­ninka. The family of the diffusible signal factor, the mechanisms for the reception of its molecular representatives, the transduction pathways and the biological effects caused by their action are characterized. A two-component system of sensory kinase RpfC/regulator RpfG, which transmits DSF-associated signals, has been identified in various bacterial pathogens, including Xanthomonas, Enterobacter, Thiobacillus, Xylella, Serratia, Leptospirillum, Stenotrophomonas, Burkholderia, Achromobacter, Yersinia, Methylobacillus, Pantoea, and Cronobacter. The intracellular sensory protein RpfR represents the DSF receptor pathway and has been identified in Burkholderia bacteria. The membrane-associated histidine kinase PA1396 carries out the reconnaissance of DSF or BDSF by the bacteria Pseudomonas aeruginosa. It is shown that the virulence level of various bacterial pathogens can be modulated by structural analogues of a diffusible signal factor. It is shown that the medicines developed on the basis of diffusible signal factors and influencing the transduction mechanisms of the intra-bacterial signal caused by them will allow solving the therapeutic task of overcoming the resistance of recurrent and chronic infectious-inflammatory diseases of the respiratory tract. A more pronounced decrease in viability formed by antibiotic-resistant bacteria Staphylococcus aureus biofilms is observed when cis-2-decenoic acid is used in combination with antibacterial agents.


Baudin M, Cinquin B, Sclavi B, Pareau D, Lopes F. Understanding the fundamental mechanisms of biofilms development and dispersal: BIAM (Biofilm Intensity and Architecture Measurement), a new tool for studying biofilms as a function of their architecture and fluorescence intensity. J Microbiol Methods. 2017 Sep;140:47-57. doi: 10.1016/j.mimet.2017.06.021.

Bi H, Yu Y, Dong H, Wang H, Cronan JE. Xanthomonas campestris RpfB is a fatty Acyl-CoA ligase required to counteract the thioesterase activity of the RpfF diffusible signal factor (DSF) synthase. Mol Microbiol. 2014 Jul;93(2):262-75. doi: 10.1111/mmi.12657.

Cai JN, Kim MA, Jung JE, Pandit S, Song KY, Jeon JG. Effects of combined oleic acid and fluoride at sub-MIC levels on EPS formation and viability of Streptococcus mutans UA159 biofilms. Biofouling. 2015;31(7):555-63. doi: 10.1080/08927014.2015.1076799.

Cai Z, Yuan ZH, Zhang H, et al. Fatty acid DSF binds and allosterically activates histidine kinase RpfC of phytopathogenic bacterium Xanthomonas campestris pv. campestris to regulate quorum-sensing and virulence. PLoS Pathog. 2017 Apr 3;13(4):e1006304. doi: 10.1371/journal.ppat.1006304.

Davies DG, Marques CN. A fatty acid messenger is responsible for inducing dispersion in microbial biofilms. J Bacteriol. 2009 Mar;191(5):1393-403. doi: 10.1128/JB.01214-08.

Deng Y, Schmid N, Wang C, et al. Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover. Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15479-84. doi: 10.1073/pnas.1205037109.

Deng Y, Lim A, Lee J, et al. Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens. BMC Microbiol. 2014 Feb 27;14:51. doi: 10.1186/1471-2180-14-51.

Deng Y, Liu X, Wu J, et al. The host plant metabolite glucose is the precursor of diffusible signal factor (DSF) family signals in Xanthomonas campestris. Appl Environ Microbiol. 2015 Apr;81(8):2861-8. doi: 10.1128/AEM.03813-14.

Dow JM. Diffusible signal factor-dependent quorum sensing in pathogenic bacteria and its exploitation for disease control. J Appl Microbiol. 2017 Jan;122(1):2-11. doi: 10.1111/jam.13307.

Grumezescu AM, Saviuc C, Chifiriuc MC, et al. Inhibitory activity of Fe(3) O(4)/oleic acid/usnic acid-core/shell/extra-shell nanofluid on S. aureus biofilm development. IEEE Trans Nanobioscience. 2011 Dec;10(4):269-74. doi: 10.1109/TNB.2011.2178263.

Guilhen C, Forestier C, Balestrino D. Biofilm dispersal: multiple elaborate strategies for dissemination of bacteria with unique properties. Mol Microbiol. 2017 Jul;105(2):188-210. doi: 10.1111/mmi.13698.

He YW, Xu M, Lin K, et al. Genome scale analysis of diffusible signal factor regulon in Xanthomonas campestris pv. campestris: identification of novel cell-cell communication-dependent genes and functions. Mol Microbiol. 2006 Jan;59(2):610-22. doi: 10.1111/j.1365-2958.2005.04961.x.

Jennings JA, Courtney HS, Haggard WO. Cis-2-decenoic acid inhibits S. aureus growth and biofilm in vitro: a pilot study. Clin Orthop Relat Res. 2012 Oct;470(10):2663-70. doi: 10.1007/s11999-012-2388-2.

Kaplan JB. Biofilm dispersal: mechanisms, clinical implications, and potential therapeutic uses. J Dent Res. 2010 Mar;89(3):205-18. doi: 10.1177/0022034509359403.

Kenny JG, Ward D, Josefsson E, et al. The Staphylococcus aureus response to unsaturated long chain free fatty acids: survival mechanisms and virulence implications. PLoS One. 2009;4(2):e4344. doi: 10.1371/journal.pone.0004344.

Le PNT, Desbois AP. Antibacterial Effect of Eicosapentaenoic Acid against Bacillus cereus and Staphylococcus aureus: Killing Kinetics, Selection for Resistance, and Potential Cellular Target. Mar Drugs. 2017 Nov 1;15(11). pii: E334. doi: 10.3390/md15110334.

Liu L, Li T, Cheng XJ, et al. Structural and functional studies on Pseudomonas aeruginosa DspI: implications for its role in DSF biosynthesis. Sci Rep. 2018 Mar 2;8(1):3928. doi: 10.1038/s41598-018-22300-1.

Marques CN, Davies DG, Sauer K. Control of Biofilms with the Fatty Acid Signaling Molecule cis-2-Decenoic Acid. Pharmaceuticals (Basel). 2015 Nov 25;8(4):816-35. doi: 10.3390/ph8040816.

Marques CN, Davies DG, Sauer K. Control of Biofilms with the Fatty Acid Signaling Molecule cis-2-Decenoic Acid. Pharmaceuticals (Basel). 2015 Nov 25;8(4):816-35. doi: 10.3390/ph8040816.

Rahmani-Badi A, Sepehr S, Fallahi H, Heidari-Keshel S. Dissection of the cis-2-decenoic acid signaling network in Pseudomonas aeruginosa using microarray technique. Front Microbiol. 2015 Apr 28;6:383. doi: 10.3389/fmicb.2015.00383.

Ryan RP, An SQ, Allan JH, McCarthy Y, Dow JM. The DSF Family of Cell-Cell Signals: An Expanding Class of Bacterial Virulence Regulators. PLoS Pathog. 2015 Jul 16;11(7):e1004986. doi: 10.1371/journal.ppat.1004986.

Ryan RP, Dow JM. Intermolecular interactions between HD-GYP and GGDEF domain proteins mediate virulence-related signal transduction in Xanthomonas campestris. Virulence. 2010 Sep-Oct;1(5):404-8. doi: 10.4161/viru.1.5.12704.

Tang JL, Liu YN, Barber CE, Dow JM, Wootton JC, Daniels MJ. Genetic and molecular analysis of a cluster of rpf genes involved in positive regulation of synthesis of extracellular enzymes and polysaccharide in Xanthomonas campestris pathovar campestris. Mol Gen Genet. 1991 May;226(3):409-17. doi: 10.1007/bf00260653.

Twomey KB, O'Connell OJ, McCarthy Y, et al. Bacterial cis-2-unsaturated fatty acids found in the cystic fibrosis airway modulate virulence and persistence of Pseudomonas aeruginosa. ISME J. 2012 May;6(5):939-50. doi: 10.1038/ismej.2011.167.

Yuyama KT, Abraham WR. cis-2-Alkenoic Acids as Promising Drugs for the Control of Biofilm Infections. Med Chem. 2016;13(1):3-12. doi: 10.2174/1573406412666160506151032.

Zhou L, Wang XY, Sun S, Yang LC, Jiang BL, He YW. Identification and characterization of naturally occurring DSF-family quorum sensing signal turnover system in the phytopathogen Xanthomonas. Environ Microbiol. 2015 Nov;17(11):4646-58. doi: 10.1111/1462-2920.12999.

Zhou L, Zhang LH, Cámara M, He YW. The DSF Family of Quorum Sensing Signals: Diversity, Biosynthesis, and Turnover. Trends Microbiol. 2017 Apr;25(4):293-303. doi: 10.1016/j.tim.2016.11.013.





Review of Literature