Mohammad Reza Haeri1, Kenneth White2, Mohammad Qharebeglou3, Malek Moein Ansar4. 1. Department of Clinical Biochemistry, School of Medicine, Qom University of Medical Sciences, Qom, Iran; Institute for Health Research and Policy, London Metropolitan University, London, United Kingdom. 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
OBJECTIVES: 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.
OBJECTIVES: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.
Authors: Leena Erkkilä; Matti Jauhiainen; Kirsi Laitinen; Kristiina Haasio; Terttu Tiirola; Pekka Saikku; Maija Leinonen Journal: Antimicrob Agents Chemother Date: 2005-09 Impact factor: 5.191
Authors: Yogesh S Biradar; Sheetal Jagatap; K R Khandelwal; Smita S Singhania Journal: Evid Based Complement Alternat Med Date: 2008-03 Impact factor: 2.629