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Undecanoic Acid, Lauric Acid, and N-Tridecanoic Acid Inhibit Escherichia coli Persistence and Biofilm Formation

  • Jin, Xing (Department of Chemical and Biological Engineering, Illinois Institute of Technology) ;
  • Zhou, Jiacheng (Department of Chemical and Biological Engineering, Illinois Institute of Technology) ;
  • Richey, Gabriella (Department of Chemical and Biological Engineering, Illinois Institute of Technology) ;
  • Wang, Mengya (Department of Chemical and Biological Engineering, Illinois Institute of Technology) ;
  • Choi Hong, Sung Min (Department of Chemical and Biological Engineering, Illinois Institute of Technology) ;
  • Hong, Seok Hoon (Department of Chemical and Biological Engineering, Illinois Institute of Technology)
  • Received : 2020.08.15
  • Accepted : 2020.10.12
  • Published : 2021.01.28

Abstract

Persister cell formation and biofilms of pathogens are extensively involved in the development of chronic infectious diseases. Eradicating persister cells is challenging, owing to their tolerance to conventional antibiotics, which cannot kill cells in a metabolically dormant state. A high frequency of persisters in biofilms makes inactivating biofilm cells more difficult, because the biofilm matrix inhibits antibiotic penetration. Fatty acids may be promising candidates as antipersister or antibiofilm agents, because some fatty acids exhibit antimicrobial effects. We previously reported that fatty acid ethyl esters effectively inhibit Escherichia coli persister formation by regulating an antitoxin. In this study, we screened a fatty acid library consisting of 65 different fatty acid molecules for altered persister formation. We found that undecanoic acid, lauric acid, and N-tridecanoic acid inhibited E. coli BW25113 persister cell formation by 25-, 58-, and 44-fold, respectively. Similarly, these fatty acids repressed persisters of enterohemorrhagic E. coli EDL933. These fatty acids were all medium-chain saturated forms. Furthermore, the fatty acids repressed Enterohemorrhagic E. coli (EHEC) biofilm formation (for example, by 8-fold for lauric acid) without having antimicrobial activity. This study demonstrates that medium-chain saturated fatty acids can serve as antipersister and antibiofilm agents that may be applied to treat bacterial infections.

Keywords

References

  1. Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, et al. 2006. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol. Syst. Biol. 2: 2006.0008. https://doi.org/10.1038/msb4100050
  2. Balaban NQ, Helaine S, Lewis K, Ackermann M, Aldridge B, Andersson DI, et al. 2019. Definitions and guidelines for research on antibiotic persistence. Nat. Rev. Microbiol. 17: 441-448. https://doi.org/10.1038/s41579-019-0196-3
  3. Balcazar JL, Subirats J, Borrego CM. 2015. The role of biofilms as environmental reservoirs of antibiotic resistance. Front. Microbiol. 6: 1216. https://doi.org/10.3389/fmicb.2015.01216
  4. Brown DR. 2019. Nitrogen starvation induces persister cell formation in Escherichia coli. J. Bacteriol. 201: e00622-18. https://doi.org/10.1128/JB.00287-19
  5. Bruhn-Olszewska B, Szczepaniak P, Matuszewska E, Kuczynska-Wisnik D, Stojowska-Swedrzynska K, Moruno Algara M. et al. 2018. Physiologically distinct subpopulations formed in Escherichia coli cultures in response to heat shock. Microbiol. Res. 209: 33-42. https://doi.org/10.1016/j.micres.2018.02.002
  6. Chulluncuy R, Espiche C, Nakamoto J, Fabbretti A, Milon P. 2016. Conformational response of 30S-bound IF3 to A-site binders streptomycin and kanamycin. Antibiotics. 5: 38. https://doi.org/10.3390/antibiotics5040038
  7. Churchward CP, Alany RG, Snyder LAS. 2018. Alternative antimicrobials: the properties of fatty acids and monoglycerides. Crit. Rev. Microbiol. 44: 561-570. https://doi.org/10.1080/1040841x.2018.1467875
  8. Ciofu O, Tolker-Nielsen T. 2019. Tolerance and resistance of Pseudomonas aeruginosa biofilms to antimicrobial agents-how P. aeruginosa can escape antibiotics. Front. Microbiol. 10: 913. https://doi.org/10.3389/fmicb.2019.00913
  9. Davies DG, Marques CNH. 2009. A fatty acid messenger is responsible for inducing dispersion in microbial biofilms. J. Bacteriol. 191: 1393-1403. https://doi.org/10.1128/JB.01214-08
  10. Dayrit FM. 2015. The properties of lauric acid and their significance in coconut oil. J. Am. Oil Chem. Soc. 92: 1-15. https://doi.org/10.1007/s11746-014-2562-7
  11. Delcour AH. 2009. Outer membrane permeability and antibiotic resistance. Biochim. Biophys. Acta - Proteins Proteomics. 1794: 808-816. https://doi.org/10.1016/j.bbapap.2008.11.005
  12. Desbois AP, Smith VJ. 2010. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. Appl. Microbiol. Biotechnol. 85: 1629-1642. https://doi.org/10.1007/s00253-009-2355-3
  13. Dubois-Brissonnet F, Trotier E, Briandet R. 2016. The biofilm lifestyle involves an increase in bacterial membrane saturated fatty acids. Front. Microbiol. 7: 1673. https://doi.org/10.3389/fmicb.2016.01673
  14. Fair RJ, Tor Y. 2014. Antibiotics and bacterial resistance in the 21st century. Perspect. Medicin. Chem. 6: 25-64. https://doi.org/10.4137/pmc.s14459
  15. Fang K, Jin X, Hong SH. 2018. Probiotic Escherichia coli inhibits biofilm formation of pathogenic E. coli via extracellular activity of DegP. Sci. Rep. 8: 4939. https://doi.org/10.1038/s41598-018-23180-1
  16. Fisher RA, Gollan B, Helaine S. 2017. Persistent bacterial infections and persister cells. Nat. Rev. Microbiol. 15: 453-464. https://doi.org/10.1038/nrmicro.2017.42
  17. Flemming H-C, Wingender J, Szewzyk U, Steinberg P, Rice SA, Kjelleberg S. 2016. Biofilms: an emergent form of bacterial life. Nat. Rev. Microbiol. 14: 563-575. https://doi.org/10.1038/nrmicro.2016.94
  18. Fujita Y, Matsuoka H, Hirooka K. 2007. Regulation of fatty acid metabolism in bacteria. Mol. Microbiol. 66: 829-839. https://doi.org/10.1111/j.1365-2958.2007.05947.x
  19. Gollan B, Grabe G, Michaux C, Helaine S. 2019. Bacterial persisters and infection: past, present, and progressing. Annu. Rev. Microbiol. 73: 359-385. https://doi.org/10.1146/annurev-micro-020518-115650
  20. Goneau LW, Yeoh NS, MacDonald KW, Cadieux PA, Burton JP, Razvi H, et al. 2014. Selective target inactivation rather than global metabolic dormancy causes antibiotic tolerance in uropathogens. Antimicrob. Agents Chemother. 58: 2089-2097. https://doi.org/10.1128/AAC.02552-13
  21. Hall CW, Mah T-F. 2017. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol. Rev. 010: 276-301. https://doi.org/10.1093/femsre/fux010
  22. Jaishankar J, Srivastava P. 2017. Molecular basis of stationary phase survival and applications. Front. Microbiol. 8: 2000. https://doi.org/10.3389/fmicb.2017.02000
  23. Jimenez-Diaz L, Caballero A, Segura A. 2017. Pathways for the degradation of fatty acids in bacteria. pp. 1-23. In: Aerobic Utilization of Hydrocarbons, Oils and Lipids, Springer International Publishing.
  24. Jin, X., Kightlinger, W., Kwon, Y.-C. and Hong, S. H. 2018. Rapid production and characterization of antimicrobial colicins using Escherichia coli-based cell-free protein synthesis. Synth. Biol. 3: ysy004. https://doi.org/10.1093/synbio/ysy004
  25. Karki P, Mohiuddin SG, Kavousi P, Orman MA. 2020. Investigating the effects of osmolytes and environmental pH on bacterial persisters. Antimicrob. Agents Chemother. 64: e02393-19.
  26. Kim HS, Ham SY, Jang Y, Sun PF, Park JH, Hoon Lee, .Park HD. 2019. Linoleic acid, a plant fatty acid, controls membrane biofouling via inhibition of biofilm formation. Fuel 253: 754-761. https://doi.org/10.1016/j.fuel.2019.05.064
  27. Krzyzek P, Gosciniak G. 2018. A proposed role for diffusible signal factors in the biofilm formation and morphological transformation of Helicobacter pylori. Turk. J. Gastroenterol. 29: 7-13. https://doi.org/10.5152/tjg.2017.17349
  28. Kumar, P., Lee, J. H., Beyenal, H. and Lee, J. 2020. Fatty acids as antibiofilm and antivirulence agents. Trends Microbiol. 28: 753-768. https://doi.org/10.1016/j.tim.2020.03.014
  29. Liaw S-J, Lai H-C, Wang W-B. 2004. Modulation of swarming and virulence by fatty acids through the RsbA protein in Proteus mirabilis. Infect. Immun. 72: 6836-6845. https://doi.org/10.1128/IAI.72.12.6836-6845.2004
  30. Maisonneuve E, Gerdes K. 2014. Molecular mechanisms underlying bacterial persisters. Cell 157: 539-548. https://doi.org/10.1016/j.cell.2014.02.050
  31. Marques CNH, Davies DG, Sauer K. 2015. Control of biofilms with the fatty acid signaling molecule cis-2-decenoic acid. Pharmaceuticals 8: 816-835. https://doi.org/10.3390/ph8040816
  32. Marques CNH, Morozov A, Planzos P, Zelaya HM. 2014. The fatty acid signaling molecule cis-2-decenoic acid increases metabolic activity and reverts persister cells to an antimicrobial-susceptible state. Appl. Environ. Microbiol. 80: 6976-6991. https://doi.org/10.1128/AEM.01576-14
  33. McGaw LJ, Jager AK, van Staden J. 2002. Antibacterial effects of fatty acids and related compounds from plants. South Afr. J. Bot. 68: 417-423. https://doi.org/10.1016/s0254-6299(15)30367-7
  34. McKay SL, Portnoy DA. 2015. Ribosome hibernation facilitates tolerance of stationary-phase bacteria to aminoglycosides. Antimicrob. Agents Chemother. 59: 6992-6999. https://doi.org/10.1128/AAC.01532-15
  35. Olsen I. 2015. Biofilm-specific antibiotic tolerance and resistance. Eur. J. Clin. Microbiol. Infect. Dis. 34: 877-886. https://doi.org/10.1007/s10096-015-2323-z
  36. Petrovic S, Arsic A. 2016. Fatty acids: fatty acids. pp. 623-631. In: Encyclopedia of Food and Health, Elsevier Inc.
  37. Poole K. 2012. Stress responses as determinants of antimicrobial resistance in Gram-negative bacteria. Trends Microbiol. 20: 227-234. https://doi.org/10.1016/j.tim.2012.02.004
  38. Ranjbar R, Masoudimanesh M, Dehkordi FS, Jonaidi-Jafari N, Rahimi E. 2017. Shiga (Vero)-toxin producing Escherichia coli isolated from the hospital foods virulence factors, o-serogroups and antimicrobial resistance properties. Antimicrob. Resist. Infect. Control 6: 1-11. https://doi.org/10.1186/s13756-016-0153-0
  39. Salisbury A-M, Woo K, Sarkar S, Schultz G, Malone M, Mayer DO. et al. 2018. Tolerance of biofilms to antimicrobials and significance to antibiotic resistance in wounds. Surg. Technol. Int. 33: 59-66.
  40. Schuster CF, Mechler L, Nolle N, Krismer B, Zelder M-E, Gotz F, et al. 2015. The MazEF toxin-antitoxin system alters the β-lactam susceptibility of Staphylococcus aureus. PLoS One 10: e0126118. https://doi.org/10.1371/journal.pone.0126118
  41. Shan Y, Lazinski D, Rowe S, Camilli A, Lewis K. 2015. Genetic basis of persister tolerance to aminoglycosides in Escherichia coli. MBio 6: e00078-15.
  42. Shao X, Fang K, Medina D, Wan J, Lee JL, Hong SH. 2019. The probiotic, Leuconostoc mesenteroides, inhibits Listeria monocytogenes biofilm formation. J. Food Saf. 40: e12750.
  43. Shilling M, Matt L, Rubin E, Visitacion MP, Haller NA, Grey SF, et al. 2013. Antimicrobial effects of virgin coconut oil and its medium-chain fatty acids on Clostridium difficile. J. Med. Food 16: 1079-1085. https://doi.org/10.1089/jmf.2012.0303
  44. Silva LN, Zimmer KR, Macedo AJ, Trentin DS. 2016. Plant natural products targeting bacterial virulence factors. Chem. Rev. 116: 9162-9236. https://doi.org/10.1021/acs.chemrev.6b00184
  45. Song S, Wood TK. 2020. A primary physiological role of toxin/antitoxin systems is phage inhibition. Front. Microbiol. 11: 1895. https://doi.org/10.3389/fmicb.2020.01895
  46. Song S, Wood TK. 2020. ppGpp ribosome dimerization model for bacterial persister formation and resuscitation. Biochem. Biophys. Res. Commun. 523: 281-286. https://doi.org/10.1016/j.bbrc.2020.01.102
  47. Wang M, Fang K, Hong SMC, Kim I, Jang IS, Hong SH. 2018. Medium chain unsaturated fatty acid ethyl esters inhibit persister formation of Escherichia coli via antitoxin HipB. Appl. Microbiol. Biotechnol. 102: 8511-8524. https://doi.org/10.1007/s00253-018-9271-3
  48. Wood TK, Song S. 2020. Forming and waking dormant cells: the ppGpp ribosome dimerization persister model. Biofilm 2: 100018. https://doi.org/10.1016/j.bioflm.2019.100018
  49. Yang H-T, Chen J-W, Rathod J, Jiang Y-Z, Tsai P-J, Hung Y-P, et al. 2017. Lauric acid is an inhibitor of Clostridium difficile growth in vitro and reduces inflammation in a mouse infection model. Front. Microbiol. 8: 2635. https://doi.org/10.3389/fmicb.2017.02635
  50. Yang QE, Walsh TR. 2017. Toxin-antitoxin systems and their role in disseminating and maintaining antimicrobial resistance. FEMS Microbiol. Rev. 41: 343-353. https://doi.org/10.1093/femsre/fux006
  51. Yoon BK, Jackman JA, Valle-Gonzalez ER, Cho NJ. 2018. Antibacterial free fatty acids and monoglycerides: biological activities, experimental testing, and therapeutic applications. Int. J. Mol. Sci. 19: 1114. https://doi.org/10.3390/ijms19041114
  52. Zhou J, Velliou E, Hong SH. 2020. Investigating the effects of nisin and free fatty acid combined treatment on Listeria monocytogenes inactivation. LWT 133: 110115. https://doi.org/10.1016/j.lwt.2020.110115

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