Cholesterol suppresses antimicrobial effect of statins

Authors

1 Department of Clinical Biochemistry, School of Medicine, Qom University of Medical Sciences, Qom, Iran

2 Institute for Health Research and Policy, London Metropolitan University, London, United Kingdom

3 Islamic azad university, Qom branch, Qom-Iran

4 Department of Clinical Biochemistry, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

Abstract

Objective(s):Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins.
Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria using gel diffusion assay.
Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria.
Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

Keywords

References

1. Matsumi R, Atomi H, Driessen AJ, van der Oost J. Isoprenoid biosynthesis in Archaea--biochemical and evolutionary implications. Res Microbiol 2011; 162:39-52.
2. Heuston S, Begley M, Gahan CG, Hill C. Isoprenoid biosynthesis in bacterial pathogens. Microbiology 2012; 158:1389-1401.
3. Noh DO, Kim SH, Gilliland SE. Incorporation of cholesterol into the cellular membrane of Lactobacillus acidophilus ATCC 43121. J Dairy Sci 1997; 80:3107-3113.
4. Dambekodi PC, Gilliland SE. Incorporation of cholesterol into the cellular membrane of Bifidobacterium longum. J Dairy Sci 1998; 81:1818-1824.
5. Hildebrandt E. and McGee DJ. Helicobacter pylori lipopolysaccharide modification, Lewis antigen expression, and gastric colonization are cholesterol-dependent. BMC Microbiol 2009; 9:258.
6. Li G. Intestinal probiotics: Interactions with bile salts and reduction of cholesterol. Procedia Environ Sci 2012; 12:1180-186.
7. McGee DJ, George AE, Trainor EA, Horton KE, Hildebrandt E, Testerman TL. Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37. Antimicrob Agents Chemother 2011; 55:2897-2904.
8. Erkkilä L, Jauhiainen M, Laitinen K, Haasio K, Tiirola T, Saikku P, et al. Effect of simvastatin, an established lipid-lowering drug, on pulmonary Chlamydia pneumoniae infection in mice. Antimicrob Agents Chemother 2005; 49:3959-3962.
9. Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med 2001; 5:378-387.
10. Friesen JA, Rodwell VW. The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases. Genome Biol 2004; 5: 248.
11. Jerwood S, Cohen J. Unexpected antimicrobial effect of statins. J Antimicrob Chemother 2008; 61: 362-4.
12. Welsh AM, Kruger P, Faoagali J. Antimicrobial action of atorvastatin and rosuvastatin. Pathology 2009; 41:689-691.
13. Biradar YS, Jagatap S, Khandelwal KR, Singhania SS. Exploring of antimicrobial activity of triphala mashi an ayurvedic formulation. Evid Based Complement Alternat Med 2008; 5:107-113.
14. Begley M, Gahan CG, Hill C. The interaction between bacteria and bile. FEMS Microbiol Rev 2005; 29:625-651.
15. Tani H, Sato M, Tsuchiya H, Namikawa I. Cholesterol incorporation into Bacillus megaterium without compositional modification of membrane lipids in response to changes of the membrane functions. Current Microbiol 1993; 26:253-256.
16. Kannenberg E, Poralla K. Hopanoid biosynthesis and function in bacteria. Naturwissenschaften 1999; 86:168-176.
17. Siedenburg G, Jendrossek D. Squalene-hopene cyclases. Appl Environ Microbiol 2011; 77:3905-15.
18. Schmerk CL, Bernards MA, Valvano MA. Hopanoid production is required for low-pH tolerance, antimicrobial resistance, and motility in Burkholderia cenocepacia. J Bacteriol 2011; 193:6712–6723.
19. Smith PF, Henrikson CV. Growth inhibition of Mycoplasma by inhibitors of polyterpene biosynthe-sis and its reversal by cholesterol. J Bacteriol 1966; 91:1854-1858.
Iranian Journal of Basic Medical Sciences
Volume 18, Issue 12 - Serial Number 12
December 2015
Pages 1253-1256

Files

Share

How to cite

Statistics