New derivatives of dehydroabietic acid target planktonic and biofilm bacteria in Staphylococcus aureus and effectively disrupt bacterial membrane integrity

Manner, Suvi; Vahermo, Mikko; Skogman, Malena; Krogerus, Sara; Vuorela, Pia; Yli‐Kauhaluoma, Jari; Fallarero, Adyary; Moreira, Vânia M.

doi:10.1016/j.ejmech.2015.07.038

Cited by 39 publications

(59 citation statements)

References 30 publications

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“…Lack of Pen G potency in equally high concentrations against biofilms of various Staph. aureus strains in well-plate based assays has been reported by others groups (Amorena et al 1999;Pettit et al 2009;Ausbacher et al 2014;Manner et al 2015). This suggests that the sole presence of 400 lmol l À1 of Pen G does not trigger biofilm removal.…”

Section: -Well Plate Biofilm Assaysupporting

confidence: 65%

“…; Manner et al . ). Exposing the biofilm to Pen G first caused erosion of the biofilm and finally resulted in complete removal of the biofilm after 40, 100 or 120 min (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…; Manner et al . ). This suggests that the sole presence of 400 μ mol l −1 of Pen G does not trigger biofilm removal.…”

Section: Resultsmentioning

confidence: 97%

“…2c and videos S1 and S2). We used 400 lmol l À1 of Pen G during our biofilm experiments based upon data from previous studies where equally high concentrations had only a low to moderate impact on biofilm viability (Ausbacher et al 2014;Manner et al 2015). Exposing the biofilm to Pen G first caused erosion of the biofilm and finally resulted in complete removal of the biofilm after 40, 100 or 120 min (Fig.…”

Section: Treatment-flow-cell Biofilm Experiments and Image Analysismentioning

confidence: 99%

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Paired methods to measure biofilm killing and removal: a case study with Penicillin G treatment of Staphylococcus aureus biofilm

Ausbacher

Lorenz

Pitts

et al. 2018

Lett Appl Microbiol

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Biofilms are tolerant to antimicrobial treatments and can lead to persistent infections. Finding new anti-biofilm strategies and understanding their mode-of-action is therefore of high importance. Historically, antimicrobial testing has focused on measuring the decrease in viability. While kill data are undeniably important, measuring biofilm disruption provides equally useful information. Starting with biofilm grown in the same reactor, we paired assessment of biofilm removal using a new treatment-flow-cell and real-time microscopy with kill data collected using the single tube method (ASTM E2871). Pairing these two methods revealed efficient biofilm removal properties of Penicillin G which were not detected during efficacy testing.

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Section: -Well Plate Biofilm Assaysupporting

confidence: 65%

“…; Manner et al . ). Exposing the biofilm to Pen G first caused erosion of the biofilm and finally resulted in complete removal of the biofilm after 40, 100 or 120 min (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…; Manner et al . ). This suggests that the sole presence of 400 μ mol l −1 of Pen G does not trigger biofilm removal.…”

Section: Resultsmentioning

confidence: 97%

Section: Treatment-flow-cell Biofilm Experiments and Image Analysismentioning

confidence: 99%

See 2 more Smart Citations

Paired methods to measure biofilm killing and removal: a case study with Penicillin G treatment of Staphylococcus aureus biofilm

Ausbacher

Lorenz

Pitts

et al. 2018

Lett Appl Microbiol

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show abstract

“…The first two compounds are dehydroabietic acid (DHA) derivatives, N- (abiet-8,11,13-trien-18oyl) cyclohexyl-L-alanine and N- (abiet-8,11,13-trien-18-oyl)-D-tryptophan, coded DHA1 (shown in Figure 1a) and DHA2 (shown in Figure 1b), respectively. These two compounds were synthetically developed in [20] (coded 11 and 9b, respectively, in [20]), by combining the abietane moiety with amino acids, which had separately been shown to display anti-biofilm properties [17,[21][22][23]. Compounds DHA1 and DHA2 were both demonstrated to prevent biofilm formation as well as to effectively disassemble pre-formed S. aureus biofilms [20], and they represent the most potent abietane-type anti-biofilm agents that have been reported thus far.…”

Section: Introductionmentioning

confidence: 99%

Strategies to Prevent Biofilm Infections on Biomaterials: Effect of Novel Naturally-Derived Biofilm Inhibitors on a Competitive Colonization Model of Titanium by Staphylococcus aureus and SaOS-2 Cells

et al. 2020

Self Cite

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Biofilm-mediated infection is a major cause of bone prosthesis failure. The lack of molecules able to act in biofilms has driven research aimed at identifying new anti-biofilm agents via chemical screens. However, to be able to accommodate a large number of compounds, the testing conditions of these screenings end up being typically far from the clinical scenario. In this study, we assess the potential applicability of three previously discovered anti-biofilm compounds to be part of implanted medical devices by testing them on in vitro systems that more closely resemble the clinical scenario. To that end, we used a competition model based on the co-culture of SaOS-2 mammalian cells and Staphylococcus aureus (collection and clinical strains) on a titanium surface, as well as titanium pre-conditioned with high serum protein concentration. Additionally, we studied whether these compounds enhance the previously proven protective effect of pre-incubating titanium with SaOS-2 cells. Out of the three, DHA1 was the one with the highest potential, showing a preventive effect on bacterial adherence in all tested conditions, making it the most promising agent for incorporation into bone implants. This study emphasizes and demonstrates the importance of using meaningful experimental models, where potential antimicrobials ought to be tested for the protection of biomaterials in translational applications.

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Peptide dendrimers G3KL and TNS18 inhibit Pseudomonas aeruginosa biofilms

Han

Liu

et al. 2019

Appl Microbiol Biotechnol

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Herein we report that peptide dendrimers G3KL and TNS18, which were recently reported to control multidrug-resistant bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, strongly inhibit biofilm formation by P. aeruginosa PA14 below their minimum inhibitory concentration (MIC) value, under which conditions they also strongly affect swarming motility. Eradication of preformed biofilms, however, required concentrations above the MIC values. Scanning electron microscopy observation and confocal laser scanning micrographs showed that peptide dendrimers can destroy the biofilm morphological structure and thickness in a dose-dependent manner, even make the biofilm dispersed completely. Membrane potential analysis indicated that planktonic cells treated with peptide dendrimers presented an increase in fluorescence intensity, suggesting that cytoplasmic membrane could be the target of G3KL and TNS18 similarly to polymyxin B. RNA-seq analysis showed that the expressions of genes in the arnBCADTEF operon-regulating lipid A modification resulting in resistance to AMPs are differentially affected between these three compounds, suggesting that each compound targets the cell membrane but in different manner. Potent activity on planktonic cells and biofilms of P. aeruginosa suggests that peptide dendrimers G3KL and TNS18 are promising candidates of clinical development for treating infections.

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New derivatives of dehydroabietic acid target planktonic and biofilm bacteria in Staphylococcus aureus and effectively disrupt bacterial membrane integrity

Cited by 39 publications

References 30 publications

Paired methods to measure biofilm killing and removal: a case study with Penicillin G treatment of Staphylococcus aureus biofilm

Paired methods to measure biofilm killing and removal: a case study with Penicillin G treatment of Staphylococcus aureus biofilm

Strategies to Prevent Biofilm Infections on Biomaterials: Effect of Novel Naturally-Derived Biofilm Inhibitors on a Competitive Colonization Model of Titanium by Staphylococcus aureus and SaOS-2 Cells

Peptide dendrimers G3KL and TNS18 inhibit Pseudomonas aeruginosa biofilms

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