Antimicrobial action of atorvastatin and rosuvastatin

Welsh, Anne-Marie; Krüger, Peter; Faoagali, Joan

doi:10.3109/00313020903305860

Cited by 27 publications

(34 citation statements)

References 4 publications

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“…Statins have been shown to inhibit the growth of S. aureus by binding to and inhibiting the activity of its HMGR enzyme (52), and this may to some extent explain why Grampositive bacteria tend to be more sensitive to statins. However, statins can attenuate the growth of bacteria irrespective of the presence of HMGR, although the mechanism is unknown and studies have reported equivalent statin MICs in species with and without HMGR (38,39).…”

Section: Effects Of Statins On In Vitro Bacterial Growthmentioning

confidence: 99%

“…Taken together, the data suggest that the antibacterial activity of statins may be statin specific and/or strain/species specific or both. Simvastatin and atorvastatin generally appear to be more effective against S. aureus, S. pneumoniae, and enterococci than other statins (37)(38)(39)43), while three distinct simvastatin MICs were reported against S. aureus clinical isolates from the United Kingdom and Jordan as well as against typed reference strains (Table 1) (37,38,41,42). It is also noteworthy that, while the MICs of statins varied according to the statin and pathogen tested, the in vitro MICs ranged from circa 15 to 400 mg/liter, far exceeding the range of typical peak plasma concentrations of patients on oral statins, which generally range from circa 10 to 300 g/liter.…”

Section: Effects Of Statins On In Vitro Bacterial Growthmentioning

confidence: 99%

See 1 more Smart Citation

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Hennessy

Adams

Reen

et al. 2016

Antimicrob Agents Chemother

108

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bStatins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called "pleiotropic effects," which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth and in vitro and in vivo virulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents. O ne of the major undisputed clinical breakthroughs of the 20th century was the discovery of the statin family of drugs. These compounds are renowned for their ability to lower cholesterol levels and are used to treat approximately 40 million individuals with high cholesterol levels worldwide. Since the discovery of mevastatin as a metabolic product of Penicillium citrinum in 1976 (1, 2), a total of nine statins have been characterized, seven of which are approved by the FDA to treat patients with high cholesterol. Structurally, statins are characterized by the presence of a conserved lactone ring (3). This structure is present as a hydrolyzed (active) form in all statins except for mevastatin, lovastatin, and simvastatin; in those statins, the lactone ring is hydrolyzed in the liver (4). Statins can be divided into two broad classes (Fig. 1). Type 1 statins are lipophilic and possess a butyryl side chain-they are said to structurally resemble mevastatin (3). Lovastatin, pravastatin, and simvastatin are type 1 statins. Type 2 statins are classically lipophobic and are distinguished from type 1 by the replacement of the butyryl side chain with a fluorophenol group and typically possess larger side chains than type 1 statins (3). Atorvastatin, cerivastatin, fluvastatin, pitavastatin, and rosuvastatin are type 2 statins.Statins exert their cholesterol-lowering effect by binding to the active site of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR), a rate-limiting enzyme involved in cholesterol biosynthesis (3). HMGR is an integral part of the mevalonate pathway, which not only is essential for cholesterol biosynthesis but also contributes to the production of isoprenoids, lipid compounds that are essential for cell signaling and structure. As well as inhibition of cholesterol, statins have also been found to have a number of cholesterol-independent, socalled "pleiotropic" effects. Statins have been reported to confer anti-inflammatory, immunomodulatory, and anticancer effects on host cells, and these effects are well characterized (5-9). Furthermore, several studies have explored the pleiotropic effects of statins in combating multisystem microbial infections, such as sepsis and pneumonia, and a growing number of studies are demonstrating that statins can directly influence the growth and virulence of bacterial pathogens. With the global increase in antibiotic resistance to existing antib...

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Section: Effects Of Statins On In Vitro Bacterial Growthmentioning

confidence: 99%

Section: Effects Of Statins On In Vitro Bacterial Growthmentioning

confidence: 99%

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Hennessy

Adams

Reen

et al. 2016

Antimicrob Agents Chemother

108

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“…Antibacterial effects of statins have also been found [69]. Statin therapy has been shown as beneficial in the treatment of bacteremia caused by Staphylococcus aureus , possibly by interfering with the inflammation caused by the S. aureus α -toxin [70,71].…”

Section: Pleiotropic Effects Of Statinsmentioning

confidence: 99%

Novel applications of statins for bone regeneration

Shah

Werlang

Kasper

et al. 2014

National Science Review

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The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering.

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“…Apart from anti-cholesterolemic property, these hypocholesterolemic drugs possess anti-oxidation, antiproliferation, anti-cancer, anti-inflammatory, anti-diabetic, anti-atherosclerotic, and anti-angiogenic properties. Also, these compounds were efficacious in the treatment of cardiovascular disease (CVD), Alzheimer's disease, renal disease, cancer, bone fracture, allergic encephalomyelitis, multiple sclerosis, immune-mediated neurological disorders, and also diabetes [15,27,32,35,39,62,[66][67][68][69]. Tocotrienols possess other potential medicinal properties apart from the hypocholesterolemic effect, and are able to reduce the atherogenic apolipoprotein B, lipoprotein(a) plasma levels.…”

Section: Pleiotropic Effects Of Different Hypo-cholesterolemic Drugsmentioning

confidence: 99%

“…Lovastatin therapy can significantly reduce morbidity and mortality in diabetics [15]. Atorvastatin and rosuvastatin also have antimicrobial activity and they inhibit isoprenoid synthesis essential for the normal cell function of prokaryotes [69].…”

Section: Pleiotropic Effects Of Different Hypo-cholesterolemic Drugsmentioning

confidence: 99%

Characterization, Modes of Synthesis, and Pleiotropic Effects of Hypocholesterolemic Compounds - A Review

Seenivasan¹,

Panda

Théodore³

2011

TOEIJ

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Studies on the various cholesterol-lowering agents is one of the important areas in clinical research. Identification and characterization of potential molecules from various sources have been carried out in the past and their relationship with the enzymes which are involved in the cholesterol cascade is gaining interest. In this review, we have highlighted various inhibitors involved in the cholesterol cascade as well as cholesterol-lowering agents, viz., tocotrienol, flavonoids, phytosterols, phytostanols, statins, DADS, and synthetic compounds. The mechanism of action and characterization of these hypocholesterolemic compounds are discussed in this communication. Major natural sources as well as synthetic and biological routes of synthesis of these compounds are reviewed in a concise manner. Especially, various HMG-CoA analogues including statins have been reviewed specifically.

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Antimicrobial action of atorvastatin and rosuvastatin

Cited by 27 publications

References 4 publications

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Novel applications of statins for bone regeneration

Characterization, Modes of Synthesis, and Pleiotropic Effects of Hypocholesterolemic Compounds - A Review

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