Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

An Innate Bactericidal Oleic Acid Effective Against Skin Infection of Methicillin-Resistant Staphylococcus aureus: A Therapy Concordant with Evolutionary Medicine

  • Chen, Chao-Hsuan (Division of Dermatology, Department of Medicine, University of California) ;
  • Wang, Yanhan (Division of Dermatology, Department of Medicine, University of California) ;
  • Nakatsuji, Teruaki (Division of Dermatology, Department of Medicine, University of California) ;
  • Liu, Yu-Tsueng (Moores Cancer Center, University of California) ;
  • Zouboulis, Christos C. (Department of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center) ;
  • Gallo, Richard L. (Division of Dermatology, Department of Medicine, University of California) ;
  • Zhang, Liangfang (Moores Cancer Center, University of California) ;
  • Hsieh, Ming-Fa (Department of Biomedical Engineering and R&D Center for Biomedical Microdevice Technology, Chung Yuan Christian University) ;
  • Huang, Chun-Ming (Division of Dermatology, Department of Medicine, University of California)
  • Received : 2010.11.15
  • Accepted : 2011.01.21
  • Published : 2011.04.28
Download PDF
⟨ Previous Next ⟩

Abstract

Free fatty acids (FFAs) are known to have bacteriocidal activity and are important components of the innate immune system. Many FFAs are naturally present in human and animal skin, breast milk, and in the bloodstream. Here, the therapeutic potential of FFAs against methicillin-resistant Staphylococcus aureus (MRSA) is demonstrated in cultures and in mice. Among a series of FFAs, only oleic acid (OA) (C18:1, cis-9) can effectively eliminate Staphylococcus aureus (S. aureus) through cell wall disruption. Lauric acid (LA, C12:0) and palmitic acid (PA, C16:0) do not have this ability. OA can inhibit growth of a number of Gram-positive bacteria, including hospital and community-associated MRSA at a dose that did not show any toxicity to human sebocytes. The bacteriocidal activities of FFAs were also demonstrated in vivo through injection of OA into mouse skin lesions previously infected with a strain of MRSA. In conclusion, our results suggest a promising therapeutic approach against MRSA through boosting the bacteriocidal activities of native FFAs, which may have been co-evolved during the interactions between microbes and their hosts.

Keywords

References

  1. Adem, P. V., C. P. Montgomery, A. N. Husain, T. K. Koogler, V. Arangelovich, M. Humilier, S. Boyle-Vavra, and R. S. Daum. 2005. Staphylococcus aureus sepsis and the Waterhouse- Friderichsen syndrome in children. N. Engl. J. Med. 353: 1245- 1251. https://doi.org/10.1056/NEJMoa044194
  2. Bakker-Woudenbera, I. A. J. M., G. Storm, and M. C. Woodle. 1994. Liposomes in the treatment of infections. J. Drug Target. 2: 363-371. https://doi.org/10.3109/10611869408996811
  3. Bergsson, G., J. Arnfinnsson, O. Steingrimsson, and H. Thormar. 2001. Killing of Gram-positive cocci by fatty acids and monoglycerides. APMIS 109: 670-678. https://doi.org/10.1034/j.1600-0463.2001.d01-131.x
  4. Bodoprost, J. and H. Rosemeyer. 2007. Analysis of phenacylester derivatives of fatty acids from human skin surface sebum by reversed-phase HPLC: Chromatographic mobility as a function of physico-chemical properties. Int. J. Mol. Sci. 8: 1111-1124. https://doi.org/10.3390/i8111111
  5. Boyle-Vavra, S. and R. S. Daum. 2007. Community-acquired methicillin-resistant Staphylococcus aureus: The role of Panton- Valentine leukocidin. Lab. Invest. 87: 3-9. https://doi.org/10.1038/labinvest.3700501
  6. Brien, S., P. Prescott, N. Bashir, H. Lewith, and G. Lewith. 2008. Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis. Osteoarthr. Cartilage 16: 1277-1288. https://doi.org/10.1016/j.joca.2008.03.002
  7. Cardoso, C. R. B., M. A. Souza, E. A. V. Ferro, S. Favoreto, and J. D. O. Pena. 2004. Influence of topical administration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds. Wound Repair Regen. 12: 235-243. https://doi.org/10.1111/j.1067-1927.2004.012216.x
  8. Clarke, S. R., R. Mohamed, L. Bian, A. F. Routh, J. F. Kokai- Kun, J. J. Mond, A. Tarkowski, and S. J. Foster. 2007. The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin. Cell Host Microbe 1: 199-212. https://doi.org/10.1016/j.chom.2007.04.005
  9. Cohen, A. L., C. Shuler, S. McAllister, G. E. Fosheim, M. G. Brown, D. Abercrombie, et al. 2007. Methamphetamine use and methicillin-resistant Staphylococcus aureus skin infections. Emerg. Infect. Dis. 13: 1707-1713. https://doi.org/10.3201/eid1311.070148
  10. de Pablo, M. A. and G. Alvarez de Cienfuegos. 2000. Modulatory effects of dietary lipids on immune system functions. Immunol. Cell Biol. 78: 31-39. https://doi.org/10.1046/j.1440-1711.2000.00875.x
  11. Desbois, A. P., T. Lebl, L. Yan, and V. J. Smith. 2008. Isolation and structural characterization of two antibacterial free fatty acids from the marine diatom, Phaeodactylum tricornutum. Appl. Microbiol. Biotechnol. 81: 755-764. https://doi.org/10.1007/s00253-008-1714-9
  12. Desbois, A. P. and V. J. Smith. 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. Diep, B. A., H. A. Carleton, R. F. Chang, G. F. Sensabaugh, and F. Perdreau-Remington. 2006. Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus. J. Infect. Dis. 193: 1495-1503. https://doi.org/10.1086/503777
  14. Fernandez-Lopez, R., C. Machon, C. M. Longshaw, S. Martin, S. Molin, E. L. Zechner, M. Espinosa, E. Lanka, and F. de la Cruz. 2005. Unsaturated fatty acids are inhibitors of bacterial conjugation. Microbiology 151: 3517-3526. https://doi.org/10.1099/mic.0.28216-0
  15. Galbraith, H. and T. B. Miller. 1973. Effect of long chain fatty acids on bacterial respiration and amino acid uptake. J. Appl. Bacteriol. 36: 659-675. https://doi.org/10.1111/j.1365-2672.1973.tb04151.x
  16. Georgel, P., K. Crozat, X. Lauth, E. Makrantonaki, H. Seltmann, S. Sovath, et al. 2005. A Toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with Gram-positive bacteria. Infect. Immun. 73: 4512-4521. https://doi.org/10.1128/IAI.73.8.4512-4521.2005
  17. Gibbons, M. A., D. M. Bowdish, D. J. Davidson, J. M. Sallenave, and A. J. Simpson. 2006. Endogenous pulmonary antibiotics. Scot. Med. J. 51: 37-42.
  18. Gilbert, M., J. MacDonald, D. Gregson, J. Siushansian, K. Zhang, S. Elsayed, et al. 2006. Outbreak in Alberta of community-acquired (USA300) methicillin-resistant Staphylococcus aureus in people with a history of drug use, homelessness or incarceration. CMAJ 175: 149-154.
  19. Goetghebeur, M., P. A. Landry, D. Han, and C. Vicente. 2007. Methicillin-resistant Staphylococcus aureus: A public health issue with economic consequences. Can. J. Infect. Dis. Med. 18: 27-34.
  20. Hackbarth, C. J. and H. F. Chambers. 1993. Blai and Blar1 regulate beta-lactamase and Pbp 2a production in methicillin- Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 37: 1144-1149. https://doi.org/10.1128/AAC.37.5.1144
  21. Hamosh, M. 1998. Protective function of proteins and lipids in human milk. Biol. Neonate 74: 163-176. https://doi.org/10.1159/000014021
  22. Heczko, P. B., R. Lutticken, W. Hryniewicz, M. Neugebauer, and G. Pulverer. 1979. Susceptibility of Staphylococcus aureus and group A, B, C, and G streptococci to Free fatty acids. J. Clin. Microbiol. 9: 333-335.
  23. Homa, D. G. and M. A. Palfreyman. 2000. Infectious diseases in the operating room. CRNA 11: 8-14.
  24. Huang, C. M., C. H. Chen, D. Pornpattananangkul, L. Zhang, M. Chan, M. F. Hsieh, and L. F. Zhang. 2011. Eradication of drug resistant Staphylococcus aureus by liposomal oleic acids. Biomaterials 32: 214-221. https://doi.org/10.1016/j.biomaterials.2010.08.076
  25. Kabara, J. J., D. Swieczkowski, A. J. Conley, and J. P. Truant. 1972. Fatty acids and derivatives as antimicrobial agents. Antimicrob. Agents Chemother. 2: 23-28. https://doi.org/10.1128/AAC.2.1.23
  26. Kabara, J. J. 1984. Antimicrobial agents derived from fatty acids. J. Am. Oil. Chem. Soc. 61: 397-403. https://doi.org/10.1007/BF02678802
  27. Kangani, C. O., D. E. Kelley, and J. P. DeLany. 2008. New method for GC/FID and GC-C-IRMS analysis of plasma free fatty acid concentration and isotopic enrichment. J. Chromatogr. B 873: 95-101. https://doi.org/10.1016/j.jchromb.2008.08.009
  28. Kaplan, S. L., K. G. Hulten, B. E. Gonzalez, W. A. Hammerman, L. Lamberth, J. Versalovic, and E. O. Mason Jr. 2005. Threeyear surveillance of community-acquired Staphylococcus aureus infections in children. Clin. Infect. Dis. 40: 1785-1791. https://doi.org/10.1086/430312
  29. Kelsey, J. A., K. W. Bayles, B. Shafii, and M. A. McGuire. 2006. Fatty acids and monoacylglycerols inhibit growth of Staphylococcus aureus. Lipids 41: 951-961. https://doi.org/10.1007/s11745-006-5048-z
  30. Kenny, J. G., D. Ward, E. Josefsson, I. M. Jonsson, J. Hinds, H. H. Rees, J. A. Lindsay, A. Tarkowski, and M. J. Horsburgh. 2009. The Staphylococcus aureus response to unsaturated long chain free fatty acids: Survival mechanisms and virulence implications. PLoS ONE 4: e4344. https://doi.org/10.1371/journal.pone.0004344
  31. Klevens, R. M., M. A. Morrison, J. Nadle, S. Petit, K. Gershman, S. Ray, et al. 2007. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298: 1763-1771. https://doi.org/10.1001/jama.298.15.1763
  32. Knapp, H. R. and M. A. Melly. 1986. Bactericidal effects of polyunsaturated fatty acids. J. Infect. Dis. 154: 84-94. https://doi.org/10.1093/infdis/154.1.84
  33. Kollef, M. H. 2009. New antimicrobial agents for methicillinresistant Staphylococcus aureus. Crit. Care Resusc. 11: 282-286.
  34. Kotani, A., Y. Hayashi, R. Matsuda, and F. Kusu. 2003. Prediction of measurement precision of apparatus using a chemometric tool in electrochemical detection of high-performance liquid chromatography. J. Chromatogr. A 986: 239-246. https://doi.org/10.1016/S0021-9673(02)02009-5
  35. Lee, C., J. Barnett, and P. D. Reaven. 1998. Liposomes enriched in oleic acid are less susceptible to oxidation and have less proinflammatory activity when exposed to oxidizing conditions. J. Lipid Res. 39: 1239-1247.
  36. Lehrer, R. I., M. Rosenman, S. S. Harwig, R. Jackson, and P. Eisenhauer. 1991. Ultrasensitive assays for endogenous antimicrobial polypeptides. J. Immunol. Methods 137: 167-173. https://doi.org/10.1016/0022-1759(91)90021-7
  37. Martin, A. and M. Clynes. 1991. Acid phosphatase: Endpoint for in vitro toxicity tests. In Vitro Cell Dev. Biol. 27A: 183- 184.
  38. Nakatsuji, T., M. C. Kao, L. Zhang, C. C. Zouboulis, R. L. Gallo, and C. M. Huang. 2010. Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating beta-defensin-2 expression. J. Invest. Dermatol. 130: 985-994. https://doi.org/10.1038/jid.2009.384
  39. Nicollier, M., T. Massengo, J. P. Remy-Martin, R. Laurent, and G. L. Adessi. 1986. Free fatty acids and fatty acids of triacylglycerols in normal and hyperkeratotic human stratum corneum. J. Invest. Dermatol. 87: 68-71. https://doi.org/10.1111/1523-1747.ep12523574
  40. Nieman, C. 1954. Influence of trace amounts of fatty acids on the growth of microorganisms. Bacteriol. Rev. 18: 147-163.
  41. Ntambi, J. M. 1995. The regulation of stearoyl-CoA desaturase (SCD). Prog. Lipid Res. 34: 139-150. https://doi.org/10.1016/0163-7827(94)00010-J
  42. Payne, D. J. 2008. Microbiology. Desperately seeking new antibiotics. Science 321: 1644-1645. https://doi.org/10.1126/science.1164586
  43. Pereira, L. M., E. Hatanaka, E. F. Martins, F. Oliveira, E. A. Liberti, S. H. Farsky, R. Curi, and T. C. Pithon-Curi. 2008. Effect of oleic and linoleic acids on the inflammatory phase of wound healing in rats. Cell Biochem. Funct. 26: 197-204. https://doi.org/10.1002/cbf.1432
  44. Peschel, A., R. W. Jack, M. Otto, L. V. Collins, P. Staubitz, G. Nicholson, et al. 2001. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine. J. Exp. Med. 193: 1067-1076. https://doi.org/10.1084/jem.193.9.1067
  45. Sado Kamdem, S., M. E. Guerzoni, J. Baranyi, and C. Pin. 2008. Effect of capric, lauric and alpha-linolenic acids on the division time distributions of single cells of Staphylococcus aureus. Int. J. Food Microbiol. 128: 122-128. https://doi.org/10.1016/j.ijfoodmicro.2008.08.002
  46. Smith, P. A. and F. E. Romesberg. 2007. Combating bacteria and drug resistance by inhibiting mechanisms of persistence and adaptation. Nat. Chem. Biol. 3: 549-556. https://doi.org/10.1038/nchembio.2007.27
  47. Speert, D. P., L. W. Wannamaker, E. D. Gray, and C. C. Clawson. 1979. Bactericidal effect of oleic acid on group A streptococci: Mechanism of action. Infect. Immun. 26: 1202-1210.
  48. Stewart, M. E. 1992. Sebaceous gland lipids. Semin. Dermatol. 11: 100-105.
  49. Takano, T., K. Saito, L. J. Teng, and T. Yamamoto. 2007. Spread of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in hospitals in Taipei, Taiwan in 2005, and comparison of its drug resistance with previous hospitalacquired MRSA. Microbiol. Immunol. 51: 627-632.
  50. Takizawa, Y., I. Taneike, S. Nakagawa, T. Oishi, Y. Nitahara, N. Iwakura, et al. 2005. A Panton-Valentine leucocidin (PVL)- positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strain, another such strain carrying a multipledrug resistance plasmid, and other more-typical PVL-negative MRSA strains found in Japan. J. Clin. Microbiol. 43: 3356-3363. https://doi.org/10.1128/JCM.43.7.3356-3363.2005
  51. Tancrede, C. 1992. Role of human microflora in health and disease. Eur. J. Clin. Microbiol. 11: 1012-1015. https://doi.org/10.1007/BF01967791
  52. Van Bambeke, F., M. P. Mingeot-Leclercq, M. J. Struelens, and P. M. Tulkens. 2008. The bacterial envelope as a target for novel anti-MRSA antibiotics. Trends Pharmacol. Sci. 29: 124-134. https://doi.org/10.1016/j.tips.2007.12.004
  53. Weigel, L. M., D. B. Clewell, S. R. Gill, N. C. Clark, L. K. McDougal, S. E. Flannagan, et al. 2003. Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science 302: 1569-1571. https://doi.org/10.1126/science.1090956
  54. Wilkinson, D. I. and J. T. Walsh. 1974. Effect of various methods of epidermal-dermal separation on distribution of acetate- C-14-labeled polyunsaturated fatty acids in skin compartments. J. Invest. Dermatol. 62: 517-521. https://doi.org/10.1111/1523-1747.ep12681061
  55. Wilson, P. C. and B. Rinker. 2009. The incidence of methicillinresistant Staphylococcus aureus in community-acquired hand infections. Ann. Plas. Surg. 62: 513-516. https://doi.org/10.1097/SAP.0b013e31818a6665
  56. Yang, D. R., D. Pornpattananangkul, T. Nakatsuji, M. Chan, D. Carson, C. M. Huang, and L. F. Zhang. 2009. The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes. Biomaterials 30: 6035-6040. https://doi.org/10.1016/j.biomaterials.2009.07.033
  57. Zesch, A. 1983. Skin irritation by topical drugs. Derm. Beruf. Umwelt. 31: 74-78.
  58. Zouboulis, C. C., H. Seltmann, H. Neitzel, and C. E. Orfanos. 1999. Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95). J. Invest. Dermatol. 113: 1011-1020. https://doi.org/10.1046/j.1523-1747.1999.00771.x

Cited by

  1. Alterations in the Porcine Colon Microbiota Induced by the Gastrointestinal Nematode Trichuris suis vol.80, pp.6, 2011, https://doi.org/10.1128/iai.00141-12
  2. Host- and microbe determinants that may influence the success of S. aureus colonization vol.2, pp.None, 2012, https://doi.org/10.3389/fcimb.2012.00056
  3. Effect of exogenous fatty acids on the growth and production of exopolysaccharides of obligately methylotrophic bacterium Methylophilus quaylei vol.48, pp.2, 2012, https://doi.org/10.1134/s0003683812020093
  4. Evaluation of the Quantitative and Qualitative Alterations in the Fatty Acid Contents of the Sebum of Patients with Inflammatory Acne during Treatment with Systemic Lymecycline and/or Oral Fatty Acid vol.2013, pp.None, 2011, https://doi.org/10.1155/2013/120475
  5. Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design vol.4, pp.None, 2011, https://doi.org/10.3389/fimmu.2013.00507
  6. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions vol.28, pp.5, 2014, https://doi.org/10.1111/jdv.12298
  7. Propionic acid and its esterified derivative suppress the growth of methicillin-resistant Staphylococcus aureus USA300 vol.5, pp.2, 2011, https://doi.org/10.3920/bm2013.0031
  8. Antibacterial Effect of Fatty Acid Salts on Oral Bacteria vol.20, pp.3, 2015, https://doi.org/10.4265/bio.20.209
  9. Combating against methicillin-resistant Staphylococcus aureus - two fatty acids from Purslane (Portulaca oleracea L.) exhibit synergistic effects with erythromycin vol.67, pp.1, 2011, https://doi.org/10.1111/jphp.12315
  10. Cholesteryl Esters Are Elevated in the Lipid Fraction of Bronchoalveolar Lavage Fluid Collected from Pediatric Cystic Fibrosis Patients vol.10, pp.4, 2011, https://doi.org/10.1371/journal.pone.0125326
  11. The role of the local microbial ecosystem in respiratory health and disease vol.370, pp.1675, 2015, https://doi.org/10.1098/rstb.2014.0294
  12. Targeting fatty acid metabolism to improve glucose metabolism vol.16, pp.9, 2015, https://doi.org/10.1111/obr.12298
  13. Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides vol.21, pp.3, 2011, https://doi.org/10.3390/molecules21030305
  14. Oxylipins produced by Pseudomonas aeruginosa promote biofilm formation and virulence vol.7, pp.1, 2011, https://doi.org/10.1038/ncomms13823
  15. Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols vol.7, pp.1, 2011, https://doi.org/10.1128/mbio.01725-15
  16. Effect of Oils Extracted from Plant Seeds on the Growth and Lipolytic Activity of Yarrowia lipolytica Yeast vol.94, pp.5, 2011, https://doi.org/10.1007/s11746-017-2975-1
  17. Selective Bactericidal Activity of Divalent Metal Salts of Lauric Acid vol.2, pp.1, 2017, https://doi.org/10.1021/acsomega.6b00279
  18. Sebaceous-immunobiology is orchestrated by sebum lipids vol.9, pp.1, 2011, https://doi.org/10.1080/19381980.2017.1375636
  19. Physicochemical and antimicrobial properties of natural rubber latex films in the presence of vegetable oil microemulsions vol.134, pp.18, 2011, https://doi.org/10.1002/app.44788
  20. Antibacterial Free Fatty Acids and Monoglycerides: Biological Activities, Experimental Testing, and Therapeutic Applications vol.19, pp.4, 2011, https://doi.org/10.3390/ijms19041114
  21. Epithelial barrier repair and prevention of allergy vol.129, pp.4, 2011, https://doi.org/10.1172/jci124608
  22. Intracellular Staphylococcus aureus Elicits the Production of Host Very Long-Chain Saturated Fatty Acids with Antimicrobial Activity vol.9, pp.7, 2011, https://doi.org/10.3390/metabo9070148
  23. A formulation of neem and hypericum oily extract for the treatment of the wound myiasis by Wohlfahrtia magnifica in domestic animals vol.118, pp.8, 2011, https://doi.org/10.1007/s00436-019-06375-x
  24. Impact of Selected Cosmetic Ingredients on Common Microorganisms of Healthy Human Skin vol.6, pp.3, 2011, https://doi.org/10.3390/cosmetics6030045
  25. Antimicrobial activity of certain natural-based plant oils against the antibiotic-resistant acne bacteria vol.27, pp.1, 2020, https://doi.org/10.1016/j.sjbs.2019.11.006
  26. Antimicrobial Activity of Host-Derived Lipids vol.9, pp.2, 2020, https://doi.org/10.3390/antibiotics9020075
  27. Excellent antimicrobial performance of co-doped magnetite double-layered ferrofluids fabricated from natural sand vol.32, pp.7, 2011, https://doi.org/10.1016/j.jksus.2020.08.009
  28. Global proteomic analysis deciphers the mechanism of action of plant derived oleic acid against Candida albicans virulence and biofilm formation vol.10, pp.None, 2011, https://doi.org/10.1038/s41598-020-61918-y
  29. The Role of Upper Airway Microbiome in the Development of Adult Asthma vol.21, pp.3, 2011, https://doi.org/10.4110/in.2021.21.e19
  30. The Selective Antibacterial Activity of the Mixed Systems Containing Myristic Acid against Staphylococci vol.70, pp.9, 2011, https://doi.org/10.5650/jos.ess21090
  31. Selective Antibacterial Activity of Palmitoleic Acid in Emulsions and Other Formulations vol.24, pp.6, 2011, https://doi.org/10.1002/jsde.12529
  32. Application of Sebum Lipidomics to Biomarkers Discovery in Neurodegenerative Diseases vol.11, pp.12, 2021, https://doi.org/10.3390/metabo11120819