DOI: 10.24075/brsmu.2018.003


Triphenyl phosphonium-based substances are alternatives to common antibiotics

Pinto TCA1, Banerjee A2, Nazarov PA3
About authors

1 Instituto de Microbiologia Paulo de Góes,
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

2 Department of Biosciences & Bioengineering,
Indian Institute of Technology Bombay, Mumbai, India

3 Belozersky Institute of Physico-Chemical Biology,
Lomonosov Moscow State University, Moscow, Russia

Correspondence should be addressed: Pavel Nazarov
ul. Narimanovskaya, d. 22, k. 3, kv. 294, Moscow, Russia, 107564; moc.liamg@apvorazan

About paper

Acknowledgements: we are grateful to Dr. Y. N. Antonenko and Dr. M. V. Skulachev for critical reading and helpful discussion of the manuscript.

Received: 2018-01-23 Accepted: 2018-02-01 Published online: 04.03.2018
  1. World Health Organization. Global action plan on antimicrobial resistance. Geneva, Switzerland: WHO Document Production Services; 2015. 21 p. Available from:
  2. World Health Organization [Internet]. c2018– [cited 2018 Jan] Antibiotic-resistant priority pathogens list. Available from:
  3. Parsek MR, Singh PK. Bacterial biofilms: an emerging link to disease pathogenesis. Annu Rev Microbiol. 2003; 57: 677–701. DOI: 10.1146/annerev.micro.57.030502.090720.
  4. Barrett L, Atkins B. The clinical presentation of prosthetic joint infection. J Antimicrob Chemother. 2014 Sep; 69 Suppl 1: i25–7. DOI: 10.1093/jac/dku250.
  5. Chatterjee S, Maiti P, Dey R, Kundu A, Dey R. Biofilms on indwelling urologic devices: microbes and antimicrobial management prospect. Ann Med Health Sci Res. 2014 Jan; 4 (1): 100–4. DOI: 10.4103/2141-9248.126612.
  6. Scherr TD, Heim CE, Morrison JM, Kielian T. Hiding in Plain Sight: Interplay between Staphylococcal Biofilms and Host Immunity. Front Immunol. 2014 Feb 5; 5: 37. DOI: 10.3389/fimmu.2014.00037.
  7. Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis.2008 Jun 1; 46 Suppl 5: S344–9. DOI: 10.1086/533590.
  8. Styers D, Sheehan DJ, Hogan P, Sahm DF. Laboratory-based surveillance of current antimicrobial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States. Ann Clin Microbiol Antimicrob. 2006 Feb 9; 5: 2. DOI: 10.1186/1476-0711-5-2.
  9. Peacock S.J., de Silva I., Lowy F.D. What determines nasal carriage of Staphylococcus aureus? Trends Microbiol. 2001 Dec; 9 (12): 605–10.
  10. Goyal N, Miller A, Tripathi M, Parvizi J. Methicillin-resistant Staphylococcus aureus (MRSA): colonisation and pre-operative screening. Bone Joint J. 2013 Jan; 95-B (1): 4–9. DOI: 10.1302/0301-620X.95B1.27973.
  11. Hawser SP, Bouchillon SK, Hoban DJ, Dowzicky M, Babinchak T. Rising incidence of Staphylococcus aureus with reduced susceptibility to vancomycin and susceptibility to antibiotics: a global analysis 2004-2009. Int J Antimicrob Agents. 2011 Mar; 37 (3): 219–24. DOI: 10.1016/j.ijantimicag.2010.10.029.
  12. Hidron AI, Edwards JR, Patel J, Horan TC, Dawn M, Sievert DM et al. Antimicrobial-Resistant Pathogens Associated with Healthcare-Associated Infections: Annual Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol. 2008; 29 (11): 996–1011.
  13. Hollenbeck BL, Rice LB. Intrinsic and acquired resistance mechanisms in enterococcus. Virulence. 2012 Aug 15; 3 (5): 421–33. DOI: 10.4161/viru21282.
  14. Centers for Disease Control and Prevention (CDC). Staphylococcus aureus Resistant to Vancomycin. MMWR Morb Mortal Wkly Rep. 2002 Jul 5; 51 (26): 565–7.
  15. Nguyen GC, Leung W, Weizman AV. Increased risk of vancomycin-resistant enterococcus (VRE) infection among patients hospitalized for inflammatory bowel disease in the United States. Inflamm Bowel Dis. 2011 Jun; 17 (6): 1338–42. DOI: 10.1002/ibd.21519.
  16. Whang DW, Miller LG, Partain NM, McKinnell JA. Systematic review and meta-analysis of linezolid and daptomycin for treatment of vancomycin-resistant enterococcal bloodstream infections. Antimicrob Agents Chemother. 2013 Oct; 57 (10): 5013–8. DOI: 10.1128/AAC.00714-13.
  17. Weiner LM, Fridkin SK, Aponte-Torres Z, Avery, L., Coffin N., Dudeck MA. et al. Vital Signs: Estimated Effects of a Coordinated Approach for Action to Reduce Antibiotic-Resistant Infections in Health Care Facilities. MMWR Morb Mortal Wkly Rep. 2013; 65 (26): 565–7.
  18. European Centre for Disease Prevention and Control. Invasive pneumococcal disease. In: ECDC. Annual epidemiological report for 2015. Stockholm: ECDC; 2017.
  19. Cherazard R, Epstein M, Doan TL, Salim T, Bharti S, Smith MA. Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and Clinical Implications. Am J Ther. 2017 May; 24 (3): e361–9. DOI: 10.1097/MJT.0000000000000551.
  20. Lane N. Energetics and genetics across the prokaryote-eukaryote divide. Biol Direct. 2011; 6: 35. DOI: 10.1186/1745-6150-6-35.
  21. Sojo V, Pomiankowski A, Lane N. A Bioenergetic Basis for Membrane Divergence in Archaea and Bacteria. PLoS Biol. 2014 Aug 12; 12 (8): e1001926. DOI: 10.1371/journal.pbio.1001926.
  22. Severin FF, Severina II, Antonenko YN, Rokitskaya TI, Cherepanov DA, Mokhova EN et al. Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore. Proc Natl Acad Sci U S A. 2010 Jan 12; 107 (2): 663–8. DOI: 10.1073/pnas.0910216107.
  23. Kanazawa A, Ikeda T, Endo T. Synthesis and antimicrobial activity of dimethyl- and trimethyl-substituted phosphonium salts with alkyl chains of various lengths. Antimicrob Agents Chemother. 1994 May; 38 (5): 945–52.
  24. Pernak J, Jedraszczyk J, Krysiński J. [Quaternary ammonium- and phosphonium compounds against bacteria and fungi]. Pharmazie. 1987 Oct; 42 (10): 703–4. German.
  25. Galkina I, Bakhtiyarova Y, Andriyashin V, Galkin V, Cherkasov R. Synthesis and Antimicrobial activities of phosphonium salts on basis of triphenylphosphine and 3,5-di-tert-butyl-4-hydroxybenzyl bromide. Phosphorus, Sulfur, and Silicon and Related Elements. 2013; 188: 15–8.
  26. Listvan VN, Listvan VV, Malishevskaya AV, Deineka SY. [Benzylic type triphenylphosphonium salts and their antimicrobial properties]. Zhurnal organichnoy ta farmatsevtichnoy khimii. 2008; 6 (24): 77–80. Ukranian.
  27. Martín-Rodríguez AJ, Babarro JM, Lahoz F, Sansón M, Martín VS, Norte M et al. From broad-spectrum biocides to quorum sensing disruptors and mussel repellents: antifouling profle of alkyltriphenylphosphonium salts. PLoS One. 2015 Apr 21; 10 (4): e0123652. DOI: 10.1371/journal.pone.0123652.
  28. Nikitina EV, Zeldi MI, Pugachev MV, Sapozhnikov SV, Shtyrlin NV, Kuznetsova SV, et al. Antibacterial efects of quaternary bis-phosphonium and ammonium salts of pyridoxine on Staphylococcus aureus cells: A single base hitting two distinct targets? World J Microbiol Biotechnol. 2016 Jan; 32 (1): 5. DOI: 10.1007/s11274-015-1969-0.
  29. Kelso GF, Porteous CM, Coulter CV, Hughes G, Porteous WK, Ledgerwood EC et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem. 2001 Feb 16; 276 (7): 4588–96. DOI: 10.1074/jbc.M009093200.
  30. Skulachev VP. A biochemical approach to the problem of aging: “megaproject” on membrane-penetrating ions. The first results and prospects. Biochemistry (Mosc). 2007 Dec; 72 (12): 1385–96.
  31. Khailova LS, Nazarov PA, Sumbatyan NV, Korshunova GA, Rokitskaya TI, Dedukhova VI et al. Uncoupling and toxic action of alkyltriphenylphosphonium cations on mitochondria and the bacterium Bacillus subtilis as a function of alkyl chain length. Biochemistry (Mosc). 2015 Dec; 80 (12): 1589–97. DOI: 10.1134/S000629791512007X.
  32. Nazarov PA, Osterman IA, Tokarchuk AV, Karakozova MV, Korshunova GA, Lyamzaev KG et al. Mitochondria-targeted antioxidants as highly effective antibiotics. Sci Rep. 2017 May 3; 7 (1): 1394. DOI: 10.1038/s41598-017-00802-8.
  33. Popova LB, Nosikova ES, Kotova EA, Tarasova EO, Nazarov PA, Khailova LS et al. Protonophoric action of triclosan causes calcium efflux from mitochondria, plasma membrane depolarization and bursts of miniature end-plate potentials. Biochim Biophys Acta. 2018 Jan 6; 1860 (5): 1000–7. DOI: 10.1016/j.bbamem.2018.01.008.