Antibacterial Properties of Phenolic Triterpenoids against Staphylococcus epidermidis

Abstract

Two phenolic triterpenoids, pristimerol (30 µg/mL) and 8-epi-6-deoxoblepharodol (20 µg/mL), obtained by catalytic reduction of pristimerin, exhibited bacteriostatic action against Staphylococcus epidermidis. This activity was not dependent on the inoculum size and the growth phase although it showed a stronger effect when cells were growing actively. Addition of phenolic triterpenoids to S. epidermidis cultures in the log-phase of growth led to an inhibitory effect on incorporation and uptake of radiolabeled precursors thymidine, uridine, leucine, and N-acetyl-glucosamine after 30 min of treatment. Furthermore, a clear release of UV-absorbing material and leakage of intracellular potassium were also detected. These findings, coupled with the high lipophilicity of these molecules, shown by high ClogP values, suggest that 8-epi and pristimerol are able to interact within the lipid bilayer and as a consequence cause functional alterations on the cytoplasmic membrane of S. epidermidis cells.

Key words

pristimerol - 8‐epi‐6‐deoxoblepharodol - Celastraceae - Staphylococcus epidermidis - antibacterial activity - membrane disruption

References

• 1 Bonomo R A. Multiple antibiotic-resistant bacteria in long-term-care facilities: an emerging problem in the practice of infectious diseases.  Clin Infect Dis. 2000;  31 1414-1422
• 2 Levy S B, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses.  Nat Med. 2004;  10 S122-S129
• 3 Mancino P, Ucciferri C, Falasca K, Pizzigallo E, Vecchiet J. Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis treated with linezolid.  Scand J Infect Dis. 2008;  40 67-73
• 4 De León L, Beltrán B, Moujir L. Antimicrobial activity of 6-oxophenolic triterpenoids. Mode of action against Bacillus subtilis.  Planta Med. 2005;  71 1-8
• 5 De León L, Moujir L. Activity and mechanism of the action of zeylasterone against Bacillus subtilis.  J Appl Microbiol. 2008;  104 1266-1274
• 6 Rodríguez F M, López M R, Jiménez I A, Moujir L, Ravelo A G, Bazzocchi I L. New phenolic triterpenes from Maytenus blepharodes. Semisynthesis of 6-deoxoblepharodol from pristimerin.  Tetrahedron. 2005;  61 2513-2519
• 7 Dirsch V, Wiemann W, Wagner H. Antiinflammatory activity of triterpene quinone-methides and proanthocyanidines from the stem bark of Heisteria pallida.  Engl Pharm Pharmacol Lett. 1992;  2 184-186
• 8 Kamal G M, Gunaherath B, Gunatilaka A A L. Studies on terpenoids and steroids. Part 3. Structure and synthesis of a new phenolic D : A-friedo-24-noroleanane triterpenoid, zeylasterone, from Kokoona zeylanica.  J Chem Soc [Perkin I]. 1983;  2845-2850
• 9 Yablonsky F. Alteration of membrane permeability in Bacillus subtilis by clofoctol.  J Gen Microbiol. 1983;  129 1089-1095
• 10 Chou W G, Pogell B M. Mode of action of pamamycin in Staphylococcus aureus.  Antimicrob Agents Chemother. 1981;  20 443-454
• 11 De León L, López M R, Moujir L. Antibacterial properties of zeylasterone, a triterpenoid isolated from Maytenus blepharodes, against Staphylococcus aureus.  Microbiol Res. , , advance online publication 29 January 2010
  DOI: 10.1016/j.micres.2009.12.004
• 12 Friedrich C L, Moyles D, Beveridge T J, Hancock R E. Antibacterial action of structurally diverse cationic peptides on Gram-positive bacteria.  Antimicrob Agents Chemother. 2000;  44 2086-2092
• 13 Sikkema J, Bont J A M, Poolman B. Interaction of cyclic hydrocarbons with biological membranes.  J Biol Chem. 1994;  269 8022-8028