Antimicrobial lipids: Emerging effector molecules of innate host defense

Porter, Edith; Daniel, Christoph; Alvarez, Sandy; Faull, Kym F.

doi:10.5411/wji.v5.i2.51

Cited by 14 publications

(11 citation statements)

References 96 publications

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“…In clinical and cosmetic applications, free fatty acids such as EPA could be applied topically to bolster the free fatty acids present naturally on the skin and mucosal surfaces as part of innate immunity to protect against microbial infection [ 3 , 4 , 7 , 8 , 9 , 10 ]. In addition to antimicrobial activities, EPA exerts beneficial anti-inflammatory actions [ 11 ] and has other positive attributes that would support its development as a new topical antibacterial agent, including wound healing properties [ 12 ], potency and perceived safety [ 1 , 4 , 13 ], and a suspected lack of acquired bacterial resistance mechanisms against this and other fatty acids [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Effect of Eicosapentaenoic Acid against Bacillus cereus and Staphylococcus aureus: Killing Kinetics, Selection for Resistance, and Potential Cellular Target

Desbois

2017

Marine Drugs

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Polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA; C20:5n-3), are attracting interest as possible new topical antibacterial agents, particularly due to their potency and perceived safety. However, relatively little is known of the underlying mechanism of antibacterial action of EPA or whether bacteria can develop resistance quickly against this or similar compounds. Therefore, the aim of this present study was to determine the mechanism of antibacterial action of EPA and investigate whether bacteria could develop reduced susceptibility to this fatty acid upon repeated exposure. Against two common Gram-positive human pathogens, Bacillus cereus and Staphylococcus aureus, EPA inhibited bacterial growth with a minimum inhibitory concentration of 64 mg/L, while minimum bactericidal concentrations were 64 mg/L and 128 mg/L for B. cereus and S. aureus, respectively. Both species were killed completely in EPA at 128 mg/L within 15 min at 37 °C, while reduced bacterial viability was associated with increased release of 260-nm-absorbing material from the bacterial cells. Taken together, these observations suggest that EPA likely kills B. cereus and S. aureus by disrupting the cell membrane, ultimately leading to cell lysis. Serial passage of the strains in the presence of sub-inhibitory concentrations of EPA did not lead to the emergence or selection of strains with reduced susceptibility to EPA during 13 passages. This present study provides data that may support the development of EPA and other fatty acids as antibacterial agents for cosmetic and pharmaceutical applications.

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Section: Introductionmentioning

confidence: 99%

Antibacterial Effect of Eicosapentaenoic Acid against Bacillus cereus and Staphylococcus aureus: Killing Kinetics, Selection for Resistance, and Potential Cellular Target

Desbois

2017

Marine Drugs

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“…These specific and nonspecific innate immune factors include simple inorganic molecules (e.g., peroxidases, nitric oxide), complement proteins, C-reactive protein, and a variety of antimicrobial peptides (AMPs) [1,2] and enzymes (e.g., defensins, lysozyme, lactoferrin) [3]. More recently, multiple endogenous lipid groups, present on the skin, in saliva, and on mucosal surfaces, have been described based on their ability to act as antimicrobial agents [3][4][5]. The hydrophobic nature of these antimicrobial lipids (AML) contributes to impermeability of the skin, preventing water loss while naturally impeding entrance of microorganisms and most toxins, while the antimicrobial nature of these natural lipids protects the body from invasion by many pathogens and opportunistic bacteria.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Activity of Host-Derived Lipids

Fischer

2020

Antibiotics

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Host-derived lipids are increasingly recognized as antimicrobial molecules that function in innate immune activities along with antimicrobial peptides. Sphingoid bases and fatty acids found on the skin, in saliva and other body fluids, and on all mucosal surfaces, including oral mucosa, exhibit antimicrobial activity against a variety of Gram positive and Gram negative bacteria, viruses, and fungi, and reduce inflammation in animal models. Multiple studies demonstrate that the antimicrobial activity of lipids is both specific and selective. There are indications that the site of action of antimicrobial fatty acids is the bacterial membrane, while the long-chain bases may inhibit cell wall synthesis as well as interacting with bacterial membranes. Research in this area, although still sporadic, has slowly increased in the last few decades; however, we still have much to learn about antimicrobial lipid mechanisms of activity and their potential use in novel drugs or topical treatments. One important potential benefit for the use of innate antimicrobial lipids (AMLs) as antimicrobial agents is the decreased likelihood side effects with treatment. Multiple studies report that endogenous AML treatments do not induce damage to cells or tissues, often decrease inflammation, and are active against biofilms. The present review summarizes the history of antimicrobial lipids from the skin surface, including both fatty acids and sphingoid bases, in multiple human body systems and summarizes their relative activity against various microorganisms. The range of antibacterial activities of lipids present at the skin surface and in saliva is presented. Some observations relevant to mechanisms of actions are discussed, but are largely still unknown. Multiple recent studies examine the therapeutic and prophylactic uses of AMLs. Although these lipids have been repeatedly demonstrated to act as innate effector molecules, they are not yet widely accepted as such. These compiled data further support fatty acid and sphingoid base inclusion as innate effector molecules.

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“…These infections are treated with various classes of antibiotics, including agents that exert their antimicrobial action by disrupting the bacterial cell membrane, such as daptomycin [2]. Moreover, many innate immunity defence effectors that act during the early stages of infection, such as free fatty acids and cationic antimicrobial peptides (AMPs), also exert antimicrobial action through targeting the integrity and functioning of the cell membrane [3,4,5].…”

Section: Introductionmentioning

confidence: 99%

Characterisation ofStaphylococcus aureuslipids by nanoelectrospray ionisation tandem mass spectrometry (nESI-MS/MS)

Young

Desbois

Coote

et al. 2019

Preprint

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19Staphylococcus aureus is a major opportunistic pathogen that is exposed to antimicrobial 20 innate immune effectors and antibiotics that can disrupt its cell membrane. An 21 understanding of S. aureus lipid composition and its role in defending the cell against 22 validated the molecular characterization and showed the principal species present in each 33 strain were predominately anteiso-and iso-branched chain fatty acids. Though the fatty acid 34 and lipid profiles were similar between the S. aureus strains, this method was sufficiently 35 sensitive to distinguish minor differences in lipid composition. In conclusion, this nESI-36 MS/MS methodology can characterise the role of lipids in antimicrobial resistance, and may 37 even be applied to the rapid diagnosis of drug-resistant strains in the clinic. 38 3 39 101 102 6 103 Materials and methods 104 S. aureus culture and lipid extraction 105 All reagents and culture media were purchased from Sigma-Aldrich Ltd. S. aureus Newman 106 (methicillin-susceptible; MSSA), BB270 (methicillin-resistant; MRSA) and Mu50 (MRSA and 107 vancomycin intermediate-resistant) were sourced and cultured in Müller-Hinton broth as 108 described previously [22]. Briefly, each bacterial strain was prepared by inoculation of a 109 colony from an agar plate into 10 ml Müller-Hinton broth and cultured at 37°C with shaking 110 until reaching an OD 600nm = 1 (~1 × 10 9 colony-forming units [cfu]). Bacterial cells were 111 harvested (1000 × g, 10 min), washed in PBS before a repeat centrifugation and removal of 112 the supernatant. Lipids were extracted according to the Bligh-Dyer method [23], dried under 113 nitrogen, and stored at 4°C until analysis by mass spectrometry. 114 115 157

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Antimicrobial lipids: Emerging effector molecules of innate host defense

Cited by 14 publications

References 96 publications

Antibacterial Effect of Eicosapentaenoic Acid against Bacillus cereus and Staphylococcus aureus: Killing Kinetics, Selection for Resistance, and Potential Cellular Target

Antibacterial Effect of Eicosapentaenoic Acid against Bacillus cereus and Staphylococcus aureus: Killing Kinetics, Selection for Resistance, and Potential Cellular Target

Antimicrobial Activity of Host-Derived Lipids

Characterisation ofStaphylococcus aureuslipids by nanoelectrospray ionisation tandem mass spectrometry (nESI-MS/MS)

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