Are the short cationic lipopeptides bacterial membrane disruptors? Structure-Activity Relationship and molecular dynamic evaluation

Greber, Katarzyna E.; Zielińska, Joanna; Nierzwicki, Łukasz; Ciura, Krzesimir; Kawczak, Piotr; Nowakowska, Joanna; Bączek, Tomasz; Sawicki, Wiesław

doi:10.1016/j.bbamem.2018.08.013

Cited by 17 publications

(23 citation statements)

References 46 publications

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“…In previous studies, we identified very a promising compound—(C 10 ) 2 -KKKK-NH 2 —which exhibits strong antibacterial activities and low toxicity towards human cells in vitro [35,36]. In this study we have further investigated the antimicrobial activity of this compound with regard to its potential application in ophthalmology, and pre-evaluated its irritation potential via computational methods which have proved to be very useful in predicting and describing the properties of the compound [37,38,39].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Activities of Lipopeptide (C10)2-KKKK-NH2 Applied Alone and in Combination with Lens Liquids to Fight Biofilms Formed on Polystyrene Surfaces and Contact Lenses

Paduszynska

Maciejewska

Greber

et al. 2019

IJMS

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The widespread use of biomaterials such as contact lenses is associated with the development of biofilm-related infections which are very difficult to manage with standard therapies. The formation of bacterial biofilms on the surface of biomaterials is associated with increased antibiotic resistance. Owing to their promising antimicrobial potential, lipopeptides are being intensively investigated as novel antimicrobials. However, due to the relatively high toxicity exhibited by numerous compounds, a lot of attention is being paid to designing new lipopeptides with optimal biological activities. The principal aim of this study was to evaluate the potential ophthalmic application of lipopeptide (C10)2-KKKK-NH2. This lipopeptide was synthesized according to Fmoc chemistry using the solid-phase method. The antibiofilm activities of the lipopeptide, antibiotics used in ocular infections, and commercially available lens liquids were determined using the broth dilution method on polystyrene 96-well plates and contact lenses. Resazurin was applied as the cell-viability reagent. The effectiveness of the commercially available lens liquids supplemented with the lipopeptide was evaluated using the same method and materials. (C10)2-KKKK-NH2 exhibited stronger anti-biofilm properties compared to those of the tested conventional antimicrobials and showed the ability to enhance the activity of lens liquids at relatively low concentrations (4–32 mg/L). Estimation of the eye irritation potential of the lipopeptide using Toxtree software 2.6.13 suggests that the compound could be safely applied on the human eye. The results of performed experiments encourage further studies on (C10)2-KKKK-NH2 and its potential application in the prophylaxis of contact lens-related eye infections.

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Section: Introductionmentioning

confidence: 99%

Antibacterial Activities of Lipopeptide (C10)2-KKKK-NH2 Applied Alone and in Combination with Lens Liquids to Fight Biofilms Formed on Polystyrene Surfaces and Contact Lenses

Paduszynska

Maciejewska

Greber

et al. 2019

IJMS

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“…5). According to these results and Greber et al (2019), the action of lipopeptides was on the cell membrane of P. putida.…”

Section: Discussionmentioning

confidence: 69%

“…Grau-Campistany et al (2015) provided strong evidence that lipopeptides altered the bacterial membrane permeability barrier. Furthermore, Greber et al (2019) reported that lipopeptides showed a significant effect on cell membrane permeability. The difference in inhibition activity is probably due to the differences in the lipid bilayer composition between gram-positive bacteria and gram-negative bacteria.…”

Section: Discussionmentioning

confidence: 99%

Bacteriostatic effect of lipopeptides from Bacillus subtilis N-2 on Pseudomonas putida using soybean meal by solid-state fermentation

Mou

Kong

et al. 2020

Mar Life Sci Technol

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Bacillus subtilis N-2 which was isolated from natto, produced lipopeptides using soybean meal as a substrate. This work aimed to purify, identify, and determine the antibacterial mechanism of lipopeptides produced by B. subtilis N-2. The fermented product obtained by solid-state fermentation was subjected to water extraction, acid precipitation, and methanol extraction. Fractions were separated and collected using a two-step ultrafiltration method and then identified by LC-MS/MS. Mass spectrometry characterization revealed the presence of four variants of iturin A that differed according to the β-amino fatty acid chain from C 14 to C 17 as well as the amino acid positions. A new lipopeptide (m/z 1070.3) was identified and its structure was different from the previously reported lipopeptides. The lipopeptides were shown to inhibit the growth of an isolate of Pseudomonas putida, a common pathogen in decaying fish, by changing membrane permeability. These results suggest that the lipopeptides from B. subtilis N-2 could be used as a biocontrol agent in aquaculture.

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“…Additionally, the analysis regarding selected common species of concern in AI also showed that both lipopeptides clearly reduced the number of relevant Gram-negative and Gram-positive bacterial species from six (ASP w/o) to only two (C16-KKKK-NH 2 ) or one (C16-KKK-NH 2 ) compared to the controls, which are promising results for their antibacterial activity. Prior studies with similar lipopeptides support these findings, demonstrating that lipopeptides inhibit the growth of both Gram-positive and Gram-negative bacteria 48 and the overall antimicrobial activity appeared to be dependent on the length of the hydrophobic chains and the amount of lysine residues 32 .…”

Section: Bacteria Asp W/o Supplements Asp W/ C16-kkk-nh 2 Asp W/ C16-mentioning

confidence: 73%

“…Interestingly, both belonged to the group of lipopeptides with the lowest MIC against tested control bacteria 18 , 31 , suggesting, that the reason for their sperm-compatibility was not an overall lower efficiency or activity, but rather a higher and more specific target selectivity. While there is evidence in prior studies suggesting that the effect of the two selected lipopeptides results from a more complex mode of action than a simple detergent-like membrane disruption, their intricate mechanism is yet to be discovered 32 . Nevertheless, AMPs bear a high potential to be applied as additives in semen preservation, when carefully selected on the basis of their antimicrobial mechanism of action and membrane selectivity.…”

Section: Discussionmentioning

confidence: 99%

Low temperature preservation of porcine semen: influence of short antimicrobial lipopeptides on sperm quality and bacterial load

Hensel¹,

Jakop²,

Scheinpflug

et al. 2020

Sci Rep

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Antimicrobial resistance is a steadily increasing problem and poses a serious threat to global public health. Therefore, it is highly necessary to advance the development of novel antimicrobial compounds and semen preservation strategies. The aim of this study was to evaluate a low temperature, antibiotic-free preservation procedure using Androstar Premium (ASP) extender (Minitüb) with antimicrobial lipopeptides. Firstly, seven lipopeptides in two concentrations (1 × minimum inhibitory concentration (MIC)/2 × MIC) were tested on their sperm-compatibility at 17 °C. Two lipopeptides, C16-KKK-NH 2 and C16-KKKK-NH 2 , did not negatively affect sperm quality and were further evaluated for their efficiency of bacterial growth inhibition at 5 °C. Besides an overall diminution of colony forming units, both peptides showed a reduction of bacterial subcultures (n = 103) with a decrement in Gram-positive rods from 65 (ASP w/o supplements) to 39/52 (ASP w/ C16-KKK-NH 2 /C16-KKKK-NH 2), in Gram-positive cocci from 21 to 9/10 and in Gram-negative species from 17 to 8/5 total subcultures. Furthermore, lipopeptides revealed activity towards selected bacteria of potential concern in artificial insemination like Trueperella pyogenes, Alcaligenes faecalis, Pseudomonas aeruginosa (not C16-KKK-NH 2), Pasteurella sp., Providencia stuartii, Escherichia coli (not C16-KKKK-NH 2) and Streptococcus porcinus (not C16-KKKK-NH 2). Consequently, both tested lipopeptides are promising candidates for alternative antibiotic-free preservation techniques of boar semen. Spreading antimicrobial resistance is a growing problem in human and veterinary medicine, poses a serious threat to global public health 1 and should therefore be addressed in a multifaceted approach from all areas of concern, including the industry branch of artificial insemination (AI) in pigs. It has been proven, that unhindered bacterial growth has detrimental effects on several sperm quality characteristics 2 and a transmission of potential pathogens to the inseminated sow has to be prevented in order to minimize negative effects on fertility and litter size 3. Semen collection is a non-sterile process and AI doses are conventionally stored at temperatures between 16 and 18 °C to prevent cold shock injuries to the highly sensitive boar spermatozoa 4. The combination of moderate temperatures and the use of nutrient-rich semen extenders promotes bacterial growth of psychrophilic and mesophilic species 5. As a countermeasure, antibiotics like gentamicin sulphate are routinely added to boar semen preserved for AI (Council Directive, European Union, 90/429/EEC). A steadily growing portion of contaminant bacteria isolated from AI doses are resistant to antibiotics commonly used as additives in semen extenders 6 , threatening animal welfare. This has far-reaching consequences for public health because of the natural backflow of parts of the rather large-volumed AI doses after insemination 7 ,

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Are the short cationic lipopeptides bacterial membrane disruptors? Structure-Activity Relationship and molecular dynamic evaluation

Cited by 17 publications

References 46 publications

Antibacterial Activities of Lipopeptide (C10)2-KKKK-NH2 Applied Alone and in Combination with Lens Liquids to Fight Biofilms Formed on Polystyrene Surfaces and Contact Lenses

Antibacterial Activities of Lipopeptide (C10)2-KKKK-NH2 Applied Alone and in Combination with Lens Liquids to Fight Biofilms Formed on Polystyrene Surfaces and Contact Lenses

Bacteriostatic effect of lipopeptides from Bacillus subtilis N-2 on Pseudomonas putida using soybean meal by solid-state fermentation

Low temperature preservation of porcine semen: influence of short antimicrobial lipopeptides on sperm quality and bacterial load

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