Sphingosine-coating of plastic surfaces prevents ventilator-associated pneumonia

Seitz, Amy E.; Schumacher, Fabian; Baker, Jennifer E.; Soddemann, Matthias; Wilker, Barbara; Caldwell, Charles C.; Gobble, Ryan M.; Kamler, Markus; Becker, Katrin Anne; Beck, Sascha; Kleuser, Burkhard; Edwards, Michael J.; Gulbins, Erich

doi:10.1007/s00109-019-01800-1

Cited by 28 publications

(39 citation statements)

References 31 publications

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“…Overall, many recent studies have proved that sphingosine and some of its derivatives have antibacterial activity against a variety of species including, among others, P. aeruginosa , Acinetobacter baumannii , Escherichia coli , S. aureus and Streptococci species [ 42 , 44 , 46 , 47 , 49 , 50 , 51 ]. A sphingosine coating of endotracheal tubes has even recently been tested against P. aeruginosa , A. baumannii and S. aureus and it showed a great capacity to prevent bacteria adherence and protection from ventilator-associated pneumonia (VAP) in vivo [ 52 ]. A recent MoA study has reported that sphingosine causes the rapid permeabilization of the bacterial membrane of P. aeruginosa and S. aureus through the binding of sphingosine’s protonated nitrogen group with cardiolipin, a negatively charged membrane protein [ 53 ].…”

Section: Resultsmentioning

confidence: 99%

Screening of FDA-Approved Drugs Using a 384-Well Plate-Based Biofilm Platform: The Case of Fingolimod

et al. 2020

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In an effort to find new repurposed antibacterial compounds, we performed the screening of an FDA-approved compounds library against Staphylococcus aureus American Type Culture Collection (ATCC) 25923. Compounds were evaluated for their capacity to prevent both planktonic growth and biofilm formation as well as to disrupt pre-formed biofilms. One of the identified initial hits was fingolimod (FTY720), an immunomodulator approved for the treatment of multiple sclerosis, which was then selected for follow-up studies. Fingolimod displayed a potent activity against S. aureus and S. epidermidis with a minimum inhibitory concentration (MIC) within the range of 12–15 µM at which concentration killing of all the bacteria was confirmed. A time–kill kinetic study revealed that fingolimod started to drastically reduce the viable bacterial count within two hours and we showed that no resistance developed against this compound for up to 20 days. Fingolimod also displayed a high activity against Acinetobacter baumannii (MIC 25 µM) as well as a modest activity against Escherichia coli and Pseudomonas aeruginosa. In addition, fingolimod inhibited quorum sensing in Chromobacterium violaceum and might therefore target this signaling pathway in certain Gram-negative bacteria. In conclusion, we present the identification of fingolimod from a compound library and its evaluation as a potential repurposed antibacterial compound.

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Section: Resultsmentioning

confidence: 99%

Screening of FDA-Approved Drugs Using a 384-Well Plate-Based Biofilm Platform: The Case of Fingolimod

et al. 2020

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“…The molecular mechanism of sphingosine's bactericidal effect has not yet been fully resolved in detail. It is known that micellar sphingosine kills many pathogens including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, Moraxella catarrhalis, Haemophilus influenzae, Burkholderia cepacia, Neisseria meningitides, and Neisseria gonorrhoeae [9,[29][30][31][32][33][34]. It is possible that sphingosine simply kills pathogens by its biophysical properties, which would also suggest that sphingosine's antimicrobial mechanism is not prone to the development of bacterial resistance.…”

Section: Discussionmentioning

confidence: 99%

Sphingosine is able to prevent and eliminate Staphylococcus epidermidis biofilm formation on different orthopedic implant materials in vitro

et al. 2019

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Periprosthetic infection (PPI) is a devastating complication in joint replacement surgery. On the background of an aging population, the number of joint replacements and associated complications is expected to increase. The capability for biofilm formation and the increasing resistance of different microbes to antibiotics have complicated the treatment of PPI, requiring the need for the development of alternative treatment options. The bactericidal effect of the naturally occurring amino alcohol sphingosine has already been reported. In our study, we demonstrate the antimicrobial efficacy of sphingosine on three different strains of biofilm producing Staphylococcus epidermidis, representing one of the most frequent microbes involved in PPI. In an in vitro analysis, sphingosine's capability for prevention and treatment of biofilm-contamination on different common orthopedic implant surfaces was tested. Coating titanium implant samples with sphingosine not only prevented implant contamination but also revealed a significant reduction of biofilm formation on the implant surfaces by 99.942%. When testing the antimicrobial efficacy of sphingosine on sessile biofilm-grown Staphylococcus epidermidis, sphingosine solution was capable to eliminate 99.999% of the bacteria on the different implant surfaces, i.e., titanium, steel, and polymethylmethacrylate. This study provides evidence on the antimicrobial efficacy of sphingosine for both planktonic and sessile biofilm-grown Staphylococcus epidermidis on contaminated orthopedic implants. Sphingosine may provide an effective and cheap treatment option for prevention and reduction of infections in joint replacement surgery. Key messages • Here we established a novel technology for prevention of implant colonization by sphingosine-coating of orthopedic implant materials. • Sphingosine-coating of orthopedic implants prevented bacterial colonization and significantly reduced biofilm formation on implant surfaces by 99.942%. • Moreover, sphingosine solution was capable to eliminate 99.999% of sessile biofilm-grown Staphylococcus epidermidis on different orthopedic implant surfaces.

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“…Namely, these include early recognition of both carriers and infected patients ( Borer et al, 2012 ; Gorrie et al, 2017 ; Liu et al, 2019 ), and controlling the spread of pathogens with apparently still effective hand hygiene and disinfection of inanimate surfaces ( Kramer et al, 2006 ; Borer et al, 2012 ; Gorrie et al, 2017 ). Multiple studies also focus on novel approaches to prevent infections by coating endotracheal tubes and catheters with new antibacterial agents ( Caratto et al, 2017 ; Bjorling et al, 2018 ; Seitz et al, 2019 ). Such multifrontal measures to control K. pneumoniae is likely to be necessary for tempering both epidemic and non-epidemic strains.…”

Section: Discussionmentioning

confidence: 99%

Systematic Comparison of Epidemic and Non-Epidemic Carbapenem Resistant Klebsiella pneumoniae Strains

Koskinen

Penttinen

Örmälä‐Odegrip

et al. 2021

Front. Cell. Infect. Microbiol.

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Over the past few decades, extensively drug resistant (XDR) resistant Klebsiella pneumoniae has become a notable burden to healthcare all over the world. Especially carbapenemase-producing strains are problematic due to their capability to withstand even last resort antibiotics. Some sequence types (STs) of K. pneumoniae are significantly more prevalent in hospital settings in comparison to other equally resistant strains. This provokes the question whether or not there are phenotypic characteristics that may render certain K. pneumoniae more suitable for epidemic dispersal between patients, hospitals, and different environments. In this study, we selected seven epidemic and non-epidemic carbapenem resistant K. pneumoniae isolates for extensive systematic characterization for phenotypic and genotypic qualities in order to identify potential factors that precede or emerge from epidemic successfulness. Studied characteristics include growth rates and densities in different conditions (media, temperature, pH, resource levels), tolerance to alcohol and drought, inhibition between strains, ability to compensate pH, as well as various genomic features. Overall, there are clear differences between isolates, yet, only drought tolerance was found to notably associate with non-epidemic K. pneumoniae strains. We further report a preliminary study on the potential to control K. pneumoniae ST11 with an antimicrobial component produced by a non-epidemic K. pneumoniae. This component initially restricts bacterial growth, but stable resistance develops rapidly in vitro.

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Sphingosine-coating of plastic surfaces prevents ventilator-associated pneumonia

Cited by 28 publications

References 31 publications

Screening of FDA-Approved Drugs Using a 384-Well Plate-Based Biofilm Platform: The Case of Fingolimod

Screening of FDA-Approved Drugs Using a 384-Well Plate-Based Biofilm Platform: The Case of Fingolimod

Sphingosine is able to prevent and eliminate Staphylococcus epidermidis biofilm formation on different orthopedic implant materials in vitro

Systematic Comparison of Epidemic and Non-Epidemic Carbapenem Resistant Klebsiella pneumoniae Strains

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