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  • Shaqour, Bahaa; Reigada, Ines; Gorecka, Zaneta; Choinska, Emilia; Verleije, Bart; Beyers, Koen; Swieszkowski, Wojciech; Fallarero, Adyary; Cos, Paul (2020)
    Additive manufacturing technologies have been widely used in the medical field. More specifically, fused filament fabrication (FFF) 3D-printing technology has been thoroughly investigated to produce drug delivery systems. Recently, few researchers have explored the possibility of directly 3D printing such systems without the need for producing a filament which is usually the feedstock material for the printer. This was possible via direct feeding of a mixture consisting of the carrier polymer and the required drug. However, as this direct feeding approach shows limited homogenizing abilities, it is vital to investigate the effect of the pre-mixing step on the quality of the 3D printed products. Our study investigates the two commonly used mixing approaches-solvent casting and powder mixing. For this purpose, polycaprolactone (PCL) was used as the main polymer under investigation and gentamicin sulfate (GS) was selected as a reference. The produced systems' efficacy was investigated for bacterial and biofilm prevention. Our data show that the solvent casting approach offers improved drug distribution within the polymeric matrix, as was observed from micro-computed topography and scanning electron microscopy visualization. Moreover, this approach shows a higher drug release rate and thus improved antibacterial efficacy. However, there were no differences among the tested approaches in terms of thermal and mechanical properties.
  • Vahermo, Mikko; Krogerus, Sara; Nasereddin, Abdelmajeed; Kaiser, Marcel; Brun, Reto; Jaffe, Charles L.; Yli-Kauhaluoma, Jari; Moreira, Vânia M. (2016)
    Derivatives of dehydroabietic acid bearing different amino acids scaffolds have potent antiprotozoal activity against Leishmania donovani and Trypanosoma cruzi, with good to high selectivity, and can therefore be regarded as good models for further development into new drugs to fight leishmaniasis and Chagas disease. Several of the tested compounds were able to kill parasites residing inside cells, with IC50 values ranging from 2.3 to 9 mu M (L. donovani) and 1.4 to 5.8 mu M (T. cruzi), reflecting their ability to fight these infections at the relevant stage responsible for disease. One of the compounds, bearing a 3-pyridyl-Dalanine side chain, was 1.5-fold more potent against T. cruzi amastigotes residing in L6 cells than the reference compound benznidazole.
  • Vanic, Zeljka; Rukavina, Zora; Manner, Suvi; Fallarero, Adyary; Uzelac, Lidija; Kralj, Marijeta; Klaric, Daniela Amidzic; Bogdanov, Anita; Raffai, Timea; Virok, Dezso Peter; Filipovic-Grcic, Jelena; Skalko-Basnet, Natasa (2019)
    Background: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.
  • Poojari, Chetan; Wilkosz, Natalia; Lira, Rafael B.; Dimova, Rumiana; Jurkiewicz, Piotr; Petka, Rafal; Kepczynski, Mariusz; Rog, Tomasz (2019)
    1,6-Diphenyl-1,3,5-hexatriene (DPH) is one of the most commonly used fluorescent probes to study dynamical and structural properties of lipid bilayers and cellular membranes via measuring steady-state or time-resolved fluorescence anisotropy. In this study, we present a limitation in the use of DPH to predict the order of lipid acyl chains when the lipid bilayer is doped with itraconazole (ITZ), an antifungal drug. Our steady-state fluorescence anisotropy measurements showed a significant decrease in fluorescence anisotropy of DPH embedded in the ITZ-containing membrane, suggesting a substantial increase in membrane fluidity, which indirectly indicates a decrease in the order of the hydrocarbon chains. This result or its interpretation is in disagreement with the fluorescence recovery after photobleaching measurements and molecular dynamics (MD) simulation data. The results of these experiments and calculations indicate an increase in the hydrocarbon chain order. The MD simulations of the bilayer containing both ITZ and DPH provide explanations for these observations. Apparently, in the presence of the drug, the DPH molecules are pushed deeper into the hydrophobic membrane core below the lipid double bonds, and the probe predominately adopts the orientation of the ITZ molecules that is parallel to the membrane surface, instead of orienting parallel to the lipid acyl chains. For this reason, DPH anisotropy provides information related to the less ordered central region of the membrane rather than reporting the properties of the upper segments of the lipid acyl chains.
  • Zhang, Ji; Ketola, Tarmo; Örmälä, Anni-Maria; Mappes, Johanna; Laakso, Jouni (2014)
  • Douillard, Francois P.; Kant, Ravi; Ritari, Jarmo; Paulin, Lars; Palva, Airi; de Vos, Willem M. (2013)
  • Andreevskaya, Margarita; Hultman, Jenni; Johansson, Per; Laine, Pia; Paulin, Lars; Auvinen, Petri; Björkroth, Johanna (2016)
    Leuconostoc gelidum subsp. gasicomitatum is a predominant lactic acid bacterium (LAB) in spoilage microbial communities of different kinds of modified-atmosphere packaged (MAP) food products. So far, only one genome sequence of a poultry-originating type strain of this bacterium (LMG 18811T) has been available. In the current study, we present the completely sequenced and functionally annotated genome of strain KG16-1 isolated from a vegetable-based product. In addition, six other vegetable-associated strains were sequenced to study possible “niche” specificity suggested by recent multilocus sequence typing. The genome of strain KG16-1 consisted of one circular chromosome and three plasmids, which together contained 2,035 CDSs. The chromosome carried at least three prophage regions and one of the plasmids encoded a galactan degradation cluster, which might provide a survival advantage in plant-related environments. The genome comparison with LMG 18811T and six other vegetable strains suggests no major differences between the meat- and vegetable-associated strains that would explain their “niche” specificity. Finally, the comparison with the genomes of other leuconostocs highlights the distribution of functionally interesting genes across the L. gelidum strains and the genus Leuconostoc.
  • Tomašič, Tihomir; Mirt, Matic; Barančoková, Michaela; Ilaš, Janez; Zidar, Nace; Tammela, Päivi Sirpa Marjaana; Kikelj, Danijel (2017)
    Development of novel DNA gyrase B inhibitors is an important field of antibacterial drug discovery whose aim is to introduce a more effective representative of this mechanistic class into the clinic. In the present study, two new series of Escherichia coli DNA gyrase inhibitors bearing the 4,5-dibromopyrrolamide moiety have been designed and synthesized. 4,5,6,7-Tetrahydrobenzo[1,2-d] thiazole-2,6-diamine derivatives inhibited E. coli DNA gyrase in the submicromolar to low micromolar range (IC50 values between 0.891 and 10.4 mu M). Their "ring-opened" analogues, based on the 2-(2-aminothiazol-4-yl) acetic acid scaffold, displayed weaker DNA gyrase inhibition with IC50 values between 15.9 and 169 mu M. Molecular docking experiments were conducted to study the binding modes of inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.
  • Abbeloos, Elke; Pyörälä, Satu; Rajala-Schultz, Päivi; Myllys, Vesa (2018)
    The aim of this study was to determine the intramammary dose of benzylpenicillin required to maintain a concentration in the milk above the MIC for the Gram-positive bacteria that cause mastitis. The product used in this study was a commercially available procaine benzylpenicillin in an oily suspension with micronized particles. Three dose levels were used: 200,000, 300,000, and 600,000IU. Concentrations of benzylpenicillin in cow milk and plasma were determined after a single intramammary dose was administered into one quarter of each of the five cows in each treatment group. Samples were analyzed using an HPLC-MS/MS method, which was validated during the study. Concentrations in the milk were well above the MIC for the target pathogens for all doses tested. There was a linear dose-dependent increase in the mean AUCs of benzylpenicillin concentrations in plasma and milk. At the first milking, 12hr after dosing, there was a significant difference between the mean milk benzylpenicillin concentrations in cows treated with a dose of 600,000IU, and those treated with 200,000 or 300,000IU. Although this study shows a linear relationship between the dose of procaine benzylpenicillin administered and the concentration in the milk in the healthy udder, it would be useful to conduct studies on cows with mastitis to define the optimum dose and duration of intramammary treatment with benzylpenicillin.
  • Jakopin, Ziga; Ilas, Janez; Barancokova, Michaela; Brvar, Matjaz; Tammela, Paivi; Dolenc, Marija Sollner; Tomasic, Tihomir; Kikelj, Danijel (2017)
    DNA gyrase and topoisomerase IV are type IIa topoisomerases that are essential bacterial enzymes required to oversee the topological state of DNA during transcription and replication processes. Their ATPase domains, GyrB and ParE, respectively, are recognized as viable targets for small molecule inhibitors, however, no synthetic or natural product GyrB/ParE inhibitors have so far reached the clinic for use as novel antibacterial agents, except for novobiocin which was withdrawn from the market. In the present study, a series of substituted oxadiazoles have been designed and synthesized as potential DNA gyrase inhibitors. Structure-based optimization resulted in the identification of compound 35, displaying an IC50 of 1.2 mu M for Escherichia coli DNA gyrase, while also exhibiting a balanced low micromolar inhibition of E. coli topoisomerase IV and of the respective Staphylococcus aureus homologues. The most promising inhibitors identified from each series were ultimately evaluated against selected Grampositive and Gram-negative bacterial strains, of which compound 35 inhibited Enterococcus faecalis with a MIC90 of 75 mu M. Our study thus provides further insight into the structural requirements of substituted oxadiazoles for dual inhibition of DNA gyrase and topoisomerase IV. (C) 2017 Elsevier Masson SAS. All rights reserved.
  • Lebreton, Francois; van Schaik, Willem; McGuire, Abigail Manson; Godfrey, Paul; Griggs, Allison; Mazumdar, Varun; Corander, Jukka; Cheng, Lu; Saif, Sakina; Young, Sarah; Zeng, Qiandong; Wortman, Jennifer; Birren, Bruce; Willems, Rob J. L.; Earl, Ashlee M.; Gilmore, Michael S. (2013)
  • Stefani, Caroline; Gonzalez-Rodriguez, David; Senju, Yosuke; Doye, Anne; Efimova, Nadia; Janel, Sebastien; Lipuma, Justine; Tsai, Meng Chen; Hamaoui, Daniel; Maddugoda, Madhavi P.; Cochet-Escartin, Olivier; Prevost, Coline; Lafont, Frank; Svitkina, Tatyana; Lappalainen, Pekka; Bassereau, Patricia; Lemichez, Emmanuel (2017)
    Transendothelial cell macroaperture (TEM) tunnels control endothelium barrier function and are triggered by several toxins from pathogenic bacteria that provoke vascular leakage. Cellular dewetting theory predicted that a line tension of uncharacterized origin works at TEM boundaries to limit their widening. Here, by conducting high-resolution microscopy approaches we unveil the presence of an actomyosin cable encircling TEMs. We develop a theoretical cellular dewetting framework to interpret TEM physical parameters that are quantitatively determined by laser ablation experiments. This establishes the critical role of ezrin and non-muscle myosin II (NMII) in the progressive implementation of line tension. Mechanistically, fluorescence-recovery-after-photobleaching experiments point for the upstream role of ezrin in stabilizing actin filaments at the edges of TEMs, thereby favouring their crosslinking by NMIIa. Collectively, our findings ascribe to ezrin and NMIIa a critical function of enhancing line tension at the cell boundary surrounding the TEMs by promoting the formation of an actomyosin ring.
  • van Belkum, Alex; Almeida, Carina; Bardiaux, Benjamin; Barrass, Sarah V.; Butcher, Sarah J.; Caykara, Tugce; Chowdhury, Sounak; Datar, Rucha; Eastwood, Ian; Goldman, Adrian; Goyal, Manisha; Happonen, Lotta; Izadi-Pruneyre, Nadia; Jacobsen, Theis; Johnson, Pirjo H.; Kempf, Volkhard A. J.; Kiessling, Andreas; Bueno, Juan Leva; Malik, Anchal; Malmstrom, Johan; Meuskens, Ina; Milner, Paul A.; Nilges, Michael; Pamme, Nicole; Peyman, Sally A.; Rodrigues, Ligia R.; Rodriguez-Mateos, Pablo; Sande, Maria G.; Silva, Carla Joana; Stasiak, Aleksandra Cecylia; Stehle, Thilo; Thibau, Arno; Vaca, Diana J.; Linke, Dirk (2021)
    Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen-surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin-ligand interaction, supported by present high-throughput "omics" technologies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.
  • Paino, Annamari; Ahlstrand, Tuuli; Nuutila, Jari; Navickaite, Indre; Lahti, Maria; Tuominen, Heidi; Välimaa, Hannamari; Lamminmaki, Urpo; Pollanen, Marja T.; Ihalin, Riikka (2013)
  • Ahlstrand, Tuuli; Torittu, Annamari; Elovaara, Heli; Välimaa, Hannamari; Pöllänen, Marja T.; Kasvandik, Sergo; Högbom, Martin; Ihalin, Riikka (2018)
    Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43nM in static settings and 2.4M in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested -lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.
  • Fyhrquist, Nanna; Muirhead, Gareth; Prast-Nielsen, Stefanie; Jeanmougin, Marine; Olah, Peter; Skoog, Tiina; Jules-Clement, Gerome; Feld, Micha; Barrientos-Somarribas, Mauricio; Sinkko, Hanna; van den Bogaard, Ellen H.; Zeeuwen, Patrick L. J. M.; Rikken, Gijs; Schalkwijk, Joost; Niehues, Hanna; Däubener, Walter; Eller, Silvia Kathrin; Alexander, Helen; Pennino, Davide; Suomela, Sari; Tessas, Ioannis; Lybeck, Emilia; Baran, Anna M.; Darban, Hamid; Gangwar, Roopesh Singh; Gerstel, Ulrich; Jahn, Katharina; Karisola, Piia; Yan, Lee; Hansmann, Britta; Katayama, Shintaro; Meller, Stephan; Bylesjo, Max; Hupe, Philippe; Levi-Schaffer, Francesca; Greco, Dario; Ranki, Annamari; Schröder, Jens M.; Barker, Jonathan; Kere, Juha; Tsoka, Sophia; Lauerma, Antti; Soumelis, Vassili; Nestle, Frank O.; Homey, Bernhard; Andersson, Björn; Alenius, Harri (2019)
    Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
  • Lyhs, Ulrike; Frandsen, Henrik; Andersen, Birgitte; Nonnemann, Bettina; Hjulsager, Charlotte; Pedersen, Karl; Chriel, Mariann (2019)
    Background The quality of mink feed and raw ingredients affect health and growth. The objectives of this study were to examine the microbiological quality of ready-to-eat mink feed and its raw ingredients, screen the plant part of the feed for mycotoxins, and determine the hygiene of the production environment in the feed processing facilities. The results of the study are important for identification of critical steps in the feed production and for formulation of recommendations for improvements of production processes to obtain better quality feed. Feed and swab samples were taken at three Danish mink feed producers October 2016 and May 2017, respectively. Viable counts, detection of methicillin-resistant Staphylococcus aureus (MRSA), influenza virus and filamentous fungi were performed together with qualitative chemical analyses for bioactive fungal metabolites and mycotoxins. Swab samples were analyzed for total viable counts. Results Viable counts varied between 7.2 x 10(2) and 9.3 x 10(7) cfu/g in raw ingredients and between 10(7) and 10(9) cfu/cm(2) on different surfaces at the feed production facilities. A pork meat product, pork haemoglobin, pork liver and a poultry mix was found positive for MRSA, while monophasic Salmonella [4,5,12:i:-] was detected in a pork meat product. Neither MRSA nor Salmonella was detected in any ready-to-eat feed. Influenza A virus was not detected in any sample. Filamentous fungi were detected in all analysed samples of ready-to-eat feed while dihydro-demethyl-sterigmatocystin was found in almost 50% of all ready-to-eat feed samples and in 80% of the sugar beet pulp. Fumonisins and other Fusarium toxins were found especially in corn gluten meal and extruded barley and wheat. Conclusions Mink feed contained a cocktail of mycotoxins and bacteria, which may not per se cause clinical disease, but may affect organ function and animal performance and well-being.
  • Allkja, Jontana; Bjarnsholt, Thomas; Coenye, Tom; Cos, Paul; Fallarero, Adyary; Harrison, Joe J.; Lopes, Susana P.; Oliver, Antonio; Pereira, Maria Olivia; Ramage, Gordon; Shirtliff, Mark E.; Stoodley, Paul; Webb, Jeremy S.; Zaat, Sebastian A. J.; Goeres, Darla M.; Azevedo, Nuno Filipe (2020)
    The lack of reproducibility of published studies is one of the major issues facing the scientific community, and the field of biofilm microbiology has been no exception. One effective strategy against this multifaceted problem is the use of minimum information guidelines. This strategy provides a guide for authors and reviewers on the necessary information that a manuscript should include for the experiments in a study to be clearly interpreted and independently reproduced. As a result of several discussions between international groups working in the area of biofilms, we present a guideline for the spectrophotometric and fluorometric assessment of biofilm formation in microplates. This guideline has been divided into 5 main sections, each presenting a comprehensive set of recommendations. The intention of the minimum information guideline is to improve the quality of scientific communication that will augment interlaboratory reproducibility in biofilm microplate assays.
  • Pérez Tanoira, Ramón; Aarnisalo, Antti A.; Eklund, Kari; Han, Xia; Soininen, Antti; Tiainen, Veli-Matti; Esteban, Jaime; Kinnari, Teemu J. (2017)
    Background: Cells of tissues and biofilm forming bacteria compete for the living space on the surface of an implant. We hypothesized the incubation of the implant (titanium, polydimethylsiloxane, and polystyrene surface) with human cells before implantation as a strategy to prevent bacterial adhesion and biofilm formation. Methods: After 24 hours of incubation with human osteogenic sarcoma SaOS-2 cells (1x10(5) cells/mL), the materials were incubated for 4.5 hours or two days with Staphylococcus aureus in serial 1:10 dilutions of 10(8) colony-forming units/mL. The bacterial adherence and biofilm biomass on materials pre-incubated with SaOS-2 cells were compared with our previous results on materials incubated only with bacteria or in simultaneous co-culture of SaOS-2 cells and S. aureus. Fluorescent microscopy and crystal violet stain were used. The number of viable SaOS-2 and bacterial cells present was tested using colorimetric methods (MTT, LDH) and drop plate method, respectively. Results: The pre-treatment with human cells was associated with a reduction of bacterial colonization of the biomaterial at 4.5 hours and 48 hours compared with the non-pre-treated materials. The presence of bacteria decreased the number of viable human cells on all materials. (Supplementary Fig. 1; see online supplementary materials at Conclusions: These results suggest that the pre-operative incubation of prostheses with host cells could prevent infection of biomaterials.
  • Gilbert-Girard, Shella; Savijoki, Kirsi; Yli-Kauhaluoma, Jari; Fallarero, Adyary (2020)
    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 mu M 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 mu M) 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.