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Rzhepishevska, Olena IORCID iD iconorcid.org/0000-0002-7912-7447
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Publications (10 of 21) Show all publications
Rzhepishevska, O. I., Limanska, N., Galkin, M., Lacoma, A., Lundquist, M., Sokol, D., . . . Ramstedt, M. (2018). Characterization of clinically relevant model bacterial strains of Pseudomonas aeruginosa for anti-biofilm testing of materials. Acta Biomaterialia, 76, 99-107
Open this publication in new window or tab >>Characterization of clinically relevant model bacterial strains of Pseudomonas aeruginosa for anti-biofilm testing of materials
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2018 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 76, p. 99-107Article in journal (Refereed) Published
Abstract [en]

There is a great interest in developing novel anti-biofilm materials in order to decrease medical device-associated bacterial infections causing morbidity and high healthcare costs. However, the testing of novel materials is often done using bacterial lab strains that may not exhibit the same phenotype as clinically relevant strains infecting medical devices. Furthermore, no consensus of strain selection exists in the field, making results very difficult to compare between studies. In this work, 19 clinical isolates of Pseudomonas aeruginosa originating from intubated patients in an intensive care unit have been characterized and compared to the lab reference strain PAO1 and a rmlC lipopolysaccharide mutant of PAO1. The adhesion and biofilm formation was monitored, as well as cell properties such as hydrophobicity, zeta potential and motility. Two groups of isolates were observed: one with high adhesion to polymer surfaces and one with low adhesion (the latter including PAO1). Furthermore, detailed biofilm assays in a flow system were performed using five characteristic isolates from the two groups. Confocal microscopy showed that the adhesion and biofilm formation of four of these five strains could be reduced dramatically on zwitterionic surface coatings. However, one isolate with pronounced swarming colonized and formed biofilm also on the antifouling surface. We demonstrate that the biofilm properties of clinical isolates can differ greatly from that of a standard lab strain and propose two clinical model strains for testing of materials designed for prevention of biofilm formation in the respiratory tract. The methodology used could beneficially be applied for screening of other collections of pathogens to identify suitable model strains for in vitro biofilm testing.

Statement of Significance: Medical-device associated infections present a great challenge in health care. Therefore, much research is undertaken to prevent bacterial colonization of new types of biomaterials. The work described here characterizes, tests and presents a number of clinically relevant bacterial model strains for assessing biofilm formation by Pseudomonas aeruginosa. Such model strains are of importance as they may provide better predictability of lab testing protocols with respect to how well materials would perform in an infection situation in a patient. Furthermore, this study uses the strains to test the performance of polymer surfaces designed to repel bacterial adhesion and it is shown that the biofilm formation for four out of the five tested bacterial strains was reduced.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Clinical isolates, Pseudomonas aeruginosa, Antifouling, Model strain, Surface chemistry
National Category
Other Chemistry Topics
Identifiers
urn:nbn:se:umu:diva-150151 (URN)10.1016/j.actbio.2018.06.019 (DOI)000442055600010 ()29902594 (PubMedID)2-s2.0-8504885706 (Scopus ID)
Funder
Stiftelsen Olle Engkvist Byggmästare, 2014/660
Available from: 2018-07-11 Created: 2018-07-11 Last updated: 2018-09-10Bibliographically approved
Hakobyan, S., Rzhepishevska, O., Barbero, D. R. & Ramstedt, M. (2018). Functionalization of zwitterionic polymer brushes, do they remain antifouling?. Surface and Interface Analysis, 50(11), 1001-1006
Open this publication in new window or tab >>Functionalization of zwitterionic polymer brushes, do they remain antifouling?
2018 (English)In: Surface and Interface Analysis, ISSN 0142-2421, E-ISSN 1096-9918, Vol. 50, no 11, p. 1001-1006Article in journal (Refereed) Published
Abstract [en]

Polymer brushes are surface coatings that can be tailored in many ways to suit specific demands including reduction of protein and bacterial fouling of biomaterials. Previously, we reported that antifouling poly (2-(methacryloxy)ethyl)dimethyl-3-sulphopropyl ammonium hydroxide) brushes dramatically reduced formation of bacterial biofilm. We hypothesized that: (1) this brush could be efficiently functionalized with a small molecule (2-oxo-2-[N-(2,4,6-trihydroxybenzylidene)-hydrazino]-acetamide, ME0163, hydrazone) and that (2) the antifouling property would remain also after functionalization. Diblock co-polymer brushes of 2-(methacryloxy)ethyl)dimethyl-3-sulphopropyl ammonium hydroxide and poly (glycidyl methacrylate) were formed by surface-initiated atom transfer radical polymerization (SI-ATRP), and the ME0163 hydrazone was covalently bound to the surface via a ring-opening reaction. Functionalization of the surfaces was followed by X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and UV-Vis spectroscopy. The influence of temperature, reaction time, and reagent concentrations on the immobilization process was investigated. Surfaces with high degree of functionalization could be made in this way. However, the functionalization rendered the surface more hydrophobic, and the antifouling property of the brush was lost, thus, disproving the second of our starting hypotheses but corroborating the first.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-143891 (URN)10.1002/sia.6376 (DOI)000448889600005 ()
Funder
Swedish Research Council, 2011-3504The Kempe FoundationsStiftelsen Olle Engkvist Byggmästare, 2014/660
Note

SIA-17-0337.R1

Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2018-11-22Bibliographically approved
Andrii, D., Matthew, B., Ludmyla, K. & Olena, R. (2018). M/XDR‐TB treatment perspective: how to avoid mountains of pills via digital technologies [Letter to the editor]. Respirology (Carlton South. Print), 23(6), 636-637
Open this publication in new window or tab >>M/XDR‐TB treatment perspective: how to avoid mountains of pills via digital technologies
2018 (English)In: Respirology (Carlton South. Print), ISSN 1323-7799, E-ISSN 1440-1843, Vol. 23, no 6, p. 636-637Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
National Category
Other Chemistry Topics Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-147547 (URN)10.1111/resp.13311 (DOI)000433336100017 ()
Available from: 2018-05-07 Created: 2018-05-07 Last updated: 2018-06-20Bibliographically approved
Burman, M., Nikolayenskyy, V., Kontsevaya, I., Molina-Moya, B., Rzhepishevska, O. & Guglielmetti, L. (2018). Tackling the MDR-TB epidemic in Ukraine: every little helps … and much more needed [Letter to the editor]. Journal of Public Health, 40(1), 210-211
Open this publication in new window or tab >>Tackling the MDR-TB epidemic in Ukraine: every little helps … and much more needed
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2018 (English)In: Journal of Public Health, ISSN 2198-1833, E-ISSN 1613-2238, Vol. 40, no 1, p. 210-211Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Infectious Medicine Social and Clinical Pharmacy Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:umu:diva-138780 (URN)10.1093/pubmed/fdx014 (DOI)000427876000032 ()28334761 (PubMedID)
Available from: 2017-08-31 Created: 2017-08-31 Last updated: 2018-08-07Bibliographically approved
Ferreira, M., Rzhepishevska, O., Grenho, L., Malheiros, D., Gonçalves, L., Almeida, A. J., . . . Bettencourt, A. (2017). Levofloxacin-loaded bone cement delivery system: highly effective against intracellular bacteria and Staphylococcus aureus biofilms. International Journal of Pharmaceutics, 532(1), 241-248
Open this publication in new window or tab >>Levofloxacin-loaded bone cement delivery system: highly effective against intracellular bacteria and Staphylococcus aureus biofilms
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2017 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 532, no 1, p. 241-248Article in journal (Refereed) Published
Abstract [en]

Staphylococcus aureus is a major pathogen in bone associated infections due to its ability to adhere and form biofilms on bone and/or implants. Moreover, recrudescent and chronic infections have been associated with S. aureus capacity to invade and persist within osteoblast cells. With the growing need of novel therapeutic tools, this research aimed to evaluate some important key biological properties of a novel carrier system composed of acrylic bone cement (polymethylmethacrylate – PMMA), loaded with a release modulator (lactose) and an antibiotic (levofloxacin).

Levofloxacin-loaded bone cement (BC) exhibited antimicrobial effects against planktonic and biofilm forms of S. aureus (evaluated by a flow chamber system). Moreover, novel BC formulation showed high anti-bacterial intraosteoblast activity. This fact led to the conclusion that levofloxacin released from BC matrices could penetrate the cell membrane of osteoblasts and be active against S. aureus strains in the intracellular environment. Furthermore, levofloxacin-BC formulations showed no significant in vitro cytotoxicity and no allergic potential (measured by the in vivo chorioallantoic membrane assay). Our results indicate that levofloxacin-loaded BC has potential as a local antibiotic delivery system for treating S. aureus associated bone infections.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Bone-infection, Fluoroquinolone-delivery-system, Flow-chamber system, Osteoblast-infection-model, Biocompatibility
National Category
Chemical Sciences Medicinal Chemistry
Identifiers
urn:nbn:se:umu:diva-139506 (URN)10.1016/j.ijpharm.2017.08.089 (DOI)000413669700025 ()
Available from: 2017-09-15 Created: 2017-09-15 Last updated: 2018-06-09Bibliographically approved
Näsström, E., Parry, C. M., Thieu, N. T., Maude, R. R., de Jong, H. K., Fukushima, M., . . . Baker, S. (2017). Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa. eLIFE, 6, Article ID e15651.
Open this publication in new window or tab >>Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa
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2017 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e15651Article in journal (Refereed) Published
Abstract [en]

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Nasstrom et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

Place, publisher, year, edition, pages
eLife Sciences Publications, 2017
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-135532 (URN)10.7554/eLife.15651 (DOI)000400828100001 ()
Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2018-06-09Bibliographically approved
Hakobyan, S., Rzhepishevska, O., Björn, E., Boily, J.-F. & Ramstedt, M. (2016). Influence of Chelation Strength and Bacterial Uptake of Gallium Salicylidene Acylhydrazide on Biofilm Formation and Virulence by Pseudomonas aeruginosa. Journal of Inorganic Biochemistry, 160, 24-32
Open this publication in new window or tab >>Influence of Chelation Strength and Bacterial Uptake of Gallium Salicylidene Acylhydrazide on Biofilm Formation and Virulence by Pseudomonas aeruginosa
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2016 (English)In: Journal of Inorganic Biochemistry, ISSN 0162-0134, E-ISSN 1873-3344, Vol. 160, p. 24-32Article in journal (Refereed) Published
Abstract [en]

Development of antibiotic resistance in bacteria causes major challenges for our society and has prompted a great need for new and alternative treatment methods for infection. One promising approach is to target bacterial virulence using for example salicylidene acylhydrazides (hydrazones). Hydrazones coordinate metal ions such as Fe(III) and Ga(III) through a five-membered and a six-membered chelation ring. One suggested mode of action is via restricting bacterial Fe uptake. Thus, it was hypothesized that the chelating strength of these substances could be used to predict their biological activity on bacterial cells. This was investigated by comparing Ga chelation strength of two hydrazone complexes, as well as bacterial Ga uptake, biofilm formation, and virulence in the form of production and secretion of a toxin (ExoS) by Pseudomonas aeruginosa. Equilibrium constants for deprotonation and Ga(III) binding of the hydrazone N′-(5-chloro-2-hydroxy-3-methylbenzylidene)-2,4-dihydroxybenzhydrazide (ME0329), with anti-virulence effect against P. aeruginosa, were determined and compared to bacterial siderophores and the previously described Ga(III) 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (Ga-ME0163) and Ga-citrate complexes. In comparison with these two complexes, it was shown that the uptake of Ga(III) was higher from the Ga-ME0329 complex. The results further show that the Ga-ME0329 complex reduced ExoS expression and secretion to a higher extent than Ga-citrate, Ga-ME0163 or the non-coordinated hydrazone. However, the effect against biofilm formation by P. aeruginosa, by the ME0329 complex, was similar to Ga-citrate and lower than what has been reported for Ga-ME0163.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Gallium, Equilibrium constants, Virulence, Biofilm, Bacteria, UV–vis
National Category
Chemical Sciences Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-107749 (URN)10.1016/j.jinorgbio.2016.04.010 (DOI)000378965200003 ()27118030 (PubMedID)
Funder
Swedish Research Council, 2011-3504Swedish Research Council, 2012-2976
Available from: 2015-08-28 Created: 2015-08-28 Last updated: 2018-06-07Bibliographically approved
Ruhal, R., Antti, H., Rzhepishevska, O., Boulanger, N., Barbero, D. R., Wai, S. N., . . . Ramstedt, M. (2015). A multivariate approach to correlate bacterial surface properties to biofilm formation by lipopolysaccharide mutants of Pseudomonas aeruginosa. Colloids and Surfaces B: Biointerfaces, 127(0), 182-191
Open this publication in new window or tab >>A multivariate approach to correlate bacterial surface properties to biofilm formation by lipopolysaccharide mutants of Pseudomonas aeruginosa
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2015 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 127, no 0, p. 182-191Article in journal (Refereed) Published
Abstract [en]

Abstract Bacterial biofilms are involved in various medical infections and for this reason it is of great importance to better understand the process of biofilm formation in order to eradicate or mitigate it. It is a very complex process and a large range of variables have been suggested to influence biofilm formation. However, their internal importance is still not well understood. In the present study, a range of surface properties of Pseudomonas aeruginosa lipopolysaccharide mutants were studied in relation to biofilm formation measured in different kinds of multi-well plates and growth conditions in order to better understand the complexity of biofilm formation. Multivariate analysis was used to simultaneously evaluate the role of a range of physiochemical parameters under different conditions. Our results suggest the presence of serum inhibited biofilm formation due to changes in twitching motility. From the multivariate analysis it was observed that the most important parameters, positively correlated to biofilm formation on two types of plates, were high hydrophobicity, near neutral zeta potential and motility. Negative correlation was observed with cell aggregation, as well as formation of outer membrane vesicles and exopolysaccharides. This work shows that the complexity of biofilm formation can be better understood using a multivariate approach that can interpret and rank the importance of different factors being present simultaneously under several different environmental conditions, enabling a better understanding of this complex process.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Pseudomonas aeruginosa, Biofilm, LPS mutant, Multivariate analysis, Bacterial surface properties
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-100362 (URN)10.1016/j.colsurfb.2015.01.030 (DOI)000353001400024 ()25679490 (PubMedID)
Available from: 2015-03-02 Created: 2015-03-02 Last updated: 2018-06-07Bibliographically approved
Dudnyk, A., Rzhepishevska, O., Rogach, K., Kutsyna, G. & Lange, C. (2015). Multidrug-resistant tuberculosis in Ukraine at a time of military conflict [Letter to the editor]. The International Journal of Tuberculosis and Lung Disease, 19(4), 492-493
Open this publication in new window or tab >>Multidrug-resistant tuberculosis in Ukraine at a time of military conflict
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2015 (English)In: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 19, no 4, p. 492-493Article in journal, Letter (Refereed) Published
National Category
Infectious Medicine Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-102353 (URN)10.5588/ijtld.14.0940 (DOI)000351967800022 ()25860008 (PubMedID)
Available from: 2015-06-02 Created: 2015-04-23 Last updated: 2018-06-07Bibliographically approved
Trentin, D. S., Silva, D. B., Frasson, A. P., Rzhepishevska, O., da Silva, M. V., Pulcini, E. d., . . . Macedo, A. J. (2015). Natural green coating inhibits adhesion of clinically important bacteria. Scientific Reports, 5, 8287
Open this publication in new window or tab >>Natural green coating inhibits adhesion of clinically important bacteria
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, p. 8287-Article in journal (Refereed) Published
Abstract [en]

Despite many advances, biomaterial-associated infections continue to be a major clinical problem. In order to minimize bacterial adhesion, material surface modifications are currently being investigated and natural products possess large potential for the design of innovative surface coatings. We report the bioguided phytochemical investigation of Pityrocarpa moniliformis and the characterization of tannins by mass spectrometry. It was demonstrated that B-type linked proanthocyanidins-coated surfaces, here termed Green coatings, reduced Gram-positive bacterial adhesion and supported mammalian cell spreading. The proposed mechanism of bacterial attachment inhibition is based on electrostatic repulsion, high hydrophilicity and the steric hindrance provided by the coating that blocks bacterium-substratum interactions. This work shows the applicability of a prototype Green-coated surface that aims to promote necessary mammalian tissue compatibility, while reducing bacterial colonization.

Place, publisher, year, edition, pages
Nature Publishing Group, 2015
National Category
Biomaterials Science Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-100278 (URN)10.1038/srep08287 (DOI)000348903900002 ()25655943 (PubMedID)
Available from: 2015-03-06 Created: 2015-02-27 Last updated: 2018-06-07Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-7912-7447

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