TY  - CONF
AU  - Ušjak, Dušan
AU  - Novović, Katarina
AU  - Filipić, Brankica
AU  - Kojić, Milan
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena M.
AU  - Arsenović-Ranin, Nevena
AU  - Milenković, Marina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5133
UR  - https://dais.sanu.ac.rs/123456789/15263
AB  - Colistin is used as a “last resort” drug in the treatmentof carbapenem-resistant Acinetobacter baumanniiinfections. Though not the most convenient option due tothe serious side effects, this antibiotic can be very efficientif administered properly (Garnacho-Montero and Timsit,2019). However, for several years now, we are witnessinga steady emergence of colistin-resistant (ColR) strains, withthe constant threat of a sudden burst worldwide (Nowak etal., 2017). Having in mind that these strains are usuallynon-susceptible to any of the existing treatments, i.e.pandrug-resistant (PDR), the development of newtherapeutic strategies is desperately needed.In the present study, we showed that colistinsusceptibility of ColR A. baumannii strains can be fullyrestored in the presence of very low amounts of seleniumnanoparticles (SeNPs). To demonstrate potent synergisticinteractions between colistin and SeNPs, we performedcheckerboard and time-kill analyses.
PB  - Macedonian Pharmaceutical Association
C3  - Macedonian Pharmaceutical Bulletin
T1  - Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin
SP  - 295
EP  - 296
VL  - 68 (Suppl. 1)
DO  - 10.33320/maced.pharm.bull.2022.68.03.142
UR  - https://hdl.handle.net/21.15107/rcub_dais_15263
ER  - 

@conference{
author = "Ušjak, Dušan and Novović, Katarina and Filipić, Brankica and Kojić, Milan and Filipović, Nenad and Stevanović, Magdalena M. and Arsenović-Ranin, Nevena and Milenković, Marina",
year = "2022",
abstract = "Colistin is used as a “last resort” drug in the treatmentof carbapenem-resistant Acinetobacter baumanniiinfections. Though not the most convenient option due tothe serious side effects, this antibiotic can be very efficientif administered properly (Garnacho-Montero and Timsit,2019). However, for several years now, we are witnessinga steady emergence of colistin-resistant (ColR) strains, withthe constant threat of a sudden burst worldwide (Nowak etal., 2017). Having in mind that these strains are usuallynon-susceptible to any of the existing treatments, i.e.pandrug-resistant (PDR), the development of newtherapeutic strategies is desperately needed.In the present study, we showed that colistinsusceptibility of ColR A. baumannii strains can be fullyrestored in the presence of very low amounts of seleniumnanoparticles (SeNPs). To demonstrate potent synergisticinteractions between colistin and SeNPs, we performedcheckerboard and time-kill analyses.",
publisher = "Macedonian Pharmaceutical Association",
journal = "Macedonian Pharmaceutical Bulletin",
title = "Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin",
pages = "295-296",
volume = "68 (Suppl. 1)",
doi = "10.33320/maced.pharm.bull.2022.68.03.142",
url = "https://hdl.handle.net/21.15107/rcub_dais_15263"
}

Ušjak, D., Novović, K., Filipić, B., Kojić, M., Filipović, N., Stevanović, M. M., Arsenović-Ranin, N.,& Milenković, M.. (2022). Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin. in Macedonian Pharmaceutical Bulletin
Macedonian Pharmaceutical Association., 68 (Suppl. 1), 295-296.
https://doi.org/10.33320/maced.pharm.bull.2022.68.03.142
https://hdl.handle.net/21.15107/rcub_dais_15263

Ušjak D, Novović K, Filipić B, Kojić M, Filipović N, Stevanović MM, Arsenović-Ranin N, Milenković M. Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin. in Macedonian Pharmaceutical Bulletin. 2022;68 (Suppl. 1):295-296.
doi:10.33320/maced.pharm.bull.2022.68.03.142
https://hdl.handle.net/21.15107/rcub_dais_15263 .

Ušjak, Dušan, Novović, Katarina, Filipić, Brankica, Kojić, Milan, Filipović, Nenad, Stevanović, Magdalena M., Arsenović-Ranin, Nevena, Milenković, Marina, "Selenium nanoparticles render pandrug-resistant Acinetobacter  baumannii susceptible to colistin" in Macedonian Pharmaceutical Bulletin, 68 (Suppl. 1) (2022):295-296,
https://doi.org/10.33320/maced.pharm.bull.2022.68.03.142 .,
https://hdl.handle.net/21.15107/rcub_dais_15263 .

TY  - JOUR
AU  - Stevanović, Magdalena
AU  - Filipović, Nenad
AU  - Kuzmanović, Maja
AU  - Tomić, Nina
AU  - Ušjak, Dušan
AU  - Milenković, Marina
AU  - Zheng, Kai
AU  - Stampfl, Juergen
AU  - Boccaccini, Aldo
PY  - 2022
UR  - https://dais.sanu.ac.rs/123456789/13579
AB  - Multidrug-resistant bacterial strains represent an emerging global health threat and a great obstacle for bone tissue engineering. One of the major components of the extracellular matrix of the bone is a collagen protein, while selenium is an element that has antimicrobial potential, and is also important for bone metabolism and bone health. Here we represent the incorporation of selenium nanoparticles (SeNPs) synthesized by the green chemical reduction method into collagen gels to produce a composite material, collagen/SeNPs, with antimicrobial properties. The samples were comprehensively characterized by zeta potential measurements, dynamic light scattering inductively coupled plasma-mass spectrometry (ICP-MS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), optical microscopy, field-emission scanning electron microscopy (FE-SEM), and differential scanning calorimetry The cytotoxicity of the SeNPS, as well as collagen/SeNPs, was tested on the MRC-5 cells. It was revealed that collagen/SeNPS expressed a lower cytotoxic effect. Collagen/SeNPs showed significant antibacterial activity against all tested Gram-positive strains, the major causative agents of orthopedic infections as well as Candida albicans. Furthermore, three-dimensional β-tricalcium phosphate (3D-TCP) scaffolds were fabricated by a well-established 3D printing (lithography) method, and afterward preliminary coated by newly-synthesized SeNPs or collagen/SeNPs. In addition, uncoated 3D-TCP scaffolds as well as coated by collagen/SeNPs were subjected to biofilm formation. The production of Staphylococcus aureus biofilm on coated scaffolds by collagen/SeNPs was significantly reduced compared to the uncoated ones. © The Author(s) 2022.
T2  - Journal of Biomaterials Applications
T1  - Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles
SP  - 1800
EP  - 1811
VL  - 36
IS  - 10
DO  - 10.1177/08853282211073731
UR  - https://hdl.handle.net/21.15107/rcub_dais_13579
ER  - 

@article{
author = "Stevanović, Magdalena and Filipović, Nenad and Kuzmanović, Maja and Tomić, Nina and Ušjak, Dušan and Milenković, Marina and Zheng, Kai and Stampfl, Juergen and Boccaccini, Aldo",
year = "2022",
abstract = "Multidrug-resistant bacterial strains represent an emerging global health threat and a great obstacle for bone tissue engineering. One of the major components of the extracellular matrix of the bone is a collagen protein, while selenium is an element that has antimicrobial potential, and is also important for bone metabolism and bone health. Here we represent the incorporation of selenium nanoparticles (SeNPs) synthesized by the green chemical reduction method into collagen gels to produce a composite material, collagen/SeNPs, with antimicrobial properties. The samples were comprehensively characterized by zeta potential measurements, dynamic light scattering inductively coupled plasma-mass spectrometry (ICP-MS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), optical microscopy, field-emission scanning electron microscopy (FE-SEM), and differential scanning calorimetry The cytotoxicity of the SeNPS, as well as collagen/SeNPs, was tested on the MRC-5 cells. It was revealed that collagen/SeNPS expressed a lower cytotoxic effect. Collagen/SeNPs showed significant antibacterial activity against all tested Gram-positive strains, the major causative agents of orthopedic infections as well as Candida albicans. Furthermore, three-dimensional β-tricalcium phosphate (3D-TCP) scaffolds were fabricated by a well-established 3D printing (lithography) method, and afterward preliminary coated by newly-synthesized SeNPs or collagen/SeNPs. In addition, uncoated 3D-TCP scaffolds as well as coated by collagen/SeNPs were subjected to biofilm formation. The production of Staphylococcus aureus biofilm on coated scaffolds by collagen/SeNPs was significantly reduced compared to the uncoated ones. © The Author(s) 2022.",
journal = "Journal of Biomaterials Applications",
title = "Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles",
pages = "1800-1811",
volume = "36",
number = "10",
doi = "10.1177/08853282211073731",
url = "https://hdl.handle.net/21.15107/rcub_dais_13579"
}

Stevanović, M., Filipović, N., Kuzmanović, M., Tomić, N., Ušjak, D., Milenković, M., Zheng, K., Stampfl, J.,& Boccaccini, A.. (2022). Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles. in Journal of Biomaterials Applications, 36(10), 1800-1811.
https://doi.org/10.1177/08853282211073731
https://hdl.handle.net/21.15107/rcub_dais_13579

Stevanović M, Filipović N, Kuzmanović M, Tomić N, Ušjak D, Milenković M, Zheng K, Stampfl J, Boccaccini A. Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles. in Journal of Biomaterials Applications. 2022;36(10):1800-1811.
doi:10.1177/08853282211073731
https://hdl.handle.net/21.15107/rcub_dais_13579 .

Stevanović, Magdalena, Filipović, Nenad, Kuzmanović, Maja, Tomić, Nina, Ušjak, Dušan, Milenković, Marina, Zheng, Kai, Stampfl, Juergen, Boccaccini, Aldo, "Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles" in Journal of Biomaterials Applications, 36, no. 10 (2022):1800-1811,
https://doi.org/10.1177/08853282211073731 .,
https://hdl.handle.net/21.15107/rcub_dais_13579 .

TY  - JOUR
AU  - Ušjak, Dušan
AU  - Novović, Katarina
AU  - Filipić, Brankica
AU  - Kojić, Milan
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
AU  - Milenković, Marina
PY  - 2022
UR  - https://dais.sanu.ac.rs/123456789/13439
AB  - Aims: To investigate the synergistic activity of colistin and selenium nanoparticles (SeNPs) against pandrug-resistant (PDR) Ac. baumannii. Methods and Results: Chequerboard and time-kill assays were employed to ex- plore the potential synergistic interactions between colistin and SeNPs against Ac. baumannii isolates (8), previously determined as colistin-resistant (MIC range 16– 256 μg ml−1 ). Also, whole-genome sequencing (WGS) and gene expression analyses were used to elucidate the mechanisms of colistin resistance. Exceptionally strong synergistic activity (FICI range 0.004–0.035) of colistin and SeNPs against colistin- resistant isolates was revealed. Colistin (0.5 or 1 μg ml −1 ) used in combination with SeNPs (0.5 μg ml−1 ) was able to reduce initial inoculum during the first 4 h of incuba- tion, in contrast to colistin (0.5, 1 or 2 μg ml−1 ) alone. Conclusions: These findings propose colistin/SeNPs combination as a new option to fight PDR Ac. baumannii, the therapeutic possibilities of which should be proved in future in vivo studies. Significance and Impact of Study: Here we present the first evidence of synergy between colistin and selenium compounds against bacteria in general. Also, WGS and gene expression analyses provide some new insights into Ac. baumannii colistin resistance mechanisms.
PB  - John Wiley and Sons Inc
T2  - Journal of Applied Microbiology
T1  - In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles
SP  - 1197
EP  - 1206
VL  - 133
IS  - 3
DO  - 10.1111/jam.15638
UR  - https://hdl.handle.net/21.15107/rcub_dais_13439
ER  - 

@article{
author = "Ušjak, Dušan and Novović, Katarina and Filipić, Brankica and Kojić, Milan and Filipović, Nenad and Stevanović, Magdalena and Milenković, Marina",
year = "2022",
abstract = "Aims: To investigate the synergistic activity of colistin and selenium nanoparticles (SeNPs) against pandrug-resistant (PDR) Ac. baumannii. Methods and Results: Chequerboard and time-kill assays were employed to ex- plore the potential synergistic interactions between colistin and SeNPs against Ac. baumannii isolates (8), previously determined as colistin-resistant (MIC range 16– 256 μg ml−1 ). Also, whole-genome sequencing (WGS) and gene expression analyses were used to elucidate the mechanisms of colistin resistance. Exceptionally strong synergistic activity (FICI range 0.004–0.035) of colistin and SeNPs against colistin- resistant isolates was revealed. Colistin (0.5 or 1 μg ml −1 ) used in combination with SeNPs (0.5 μg ml−1 ) was able to reduce initial inoculum during the first 4 h of incuba- tion, in contrast to colistin (0.5, 1 or 2 μg ml−1 ) alone. Conclusions: These findings propose colistin/SeNPs combination as a new option to fight PDR Ac. baumannii, the therapeutic possibilities of which should be proved in future in vivo studies. Significance and Impact of Study: Here we present the first evidence of synergy between colistin and selenium compounds against bacteria in general. Also, WGS and gene expression analyses provide some new insights into Ac. baumannii colistin resistance mechanisms.",
publisher = "John Wiley and Sons Inc",
journal = "Journal of Applied Microbiology",
title = "In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles",
pages = "1197-1206",
volume = "133",
number = "3",
doi = "10.1111/jam.15638",
url = "https://hdl.handle.net/21.15107/rcub_dais_13439"
}

Ušjak, D., Novović, K., Filipić, B., Kojić, M., Filipović, N., Stevanović, M.,& Milenković, M.. (2022). In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles. in Journal of Applied Microbiology
John Wiley and Sons Inc., 133(3), 1197-1206.
https://doi.org/10.1111/jam.15638
https://hdl.handle.net/21.15107/rcub_dais_13439

Ušjak D, Novović K, Filipić B, Kojić M, Filipović N, Stevanović M, Milenković M. In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles. in Journal of Applied Microbiology. 2022;133(3):1197-1206.
doi:10.1111/jam.15638
https://hdl.handle.net/21.15107/rcub_dais_13439 .

Ušjak, Dušan, Novović, Katarina, Filipić, Brankica, Kojić, Milan, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina, "In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles" in Journal of Applied Microbiology, 133, no. 3 (2022):1197-1206,
https://doi.org/10.1111/jam.15638 .,
https://hdl.handle.net/21.15107/rcub_dais_13439 .

TY  - JOUR
AU  - Ušjak, Dušan
AU  - Novović, Katarina
AU  - Filipić, Brankica
AU  - Kojić, Milan
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
AU  - Milenković, Marina
PY  - 2022
UR  - https://dais.sanu.ac.rs/123456789/13439
UR  - https://dais.sanu.ac.rs/123456789/13449
AB  - Aims: To investigate the synergistic activity of colistin and selenium nanoparticles (SeNPs) against pandrug-resistant (PDR) Ac. baumannii. Methods and Results: Chequerboard and time-kill assays were employed to ex- plore the potential synergistic interactions between colistin and SeNPs against Ac. baumannii isolates (8), previously determined as colistin-resistant (MIC range 16– 256 μg ml−1 ). Also, whole-genome sequencing (WGS) and gene expression analyses were used to elucidate the mechanisms of colistin resistance. Exceptionally strong synergistic activity (FICI range 0.004–0.035) of colistin and SeNPs against colistin- resistant isolates was revealed. Colistin (0.5 or 1 μg ml −1 ) used in combination with SeNPs (0.5 μg ml−1 ) was able to reduce initial inoculum during the first 4 h of incuba- tion, in contrast to colistin (0.5, 1 or 2 μg ml−1 ) alone. Conclusions: These findings propose colistin/SeNPs combination as a new option to fight PDR Ac. baumannii, the therapeutic possibilities of which should be proved in future in vivo studies. Significance and Impact of Study: Here we present the first evidence of synergy between colistin and selenium compounds against bacteria in general. Also, WGS and gene expression analyses provide some new insights into Ac. baumannii colistin resistance mechanisms.
PB  - John Wiley and Sons Inc
T2  - Journal of Applied Microbiology
T1  - In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles
SP  - 1197
EP  - 1206
VL  - 133
IS  - 3
DO  - 10.1111/jam.15638
UR  - https://hdl.handle.net/21.15107/rcub_dais_13449
ER  - 

@article{
author = "Ušjak, Dušan and Novović, Katarina and Filipić, Brankica and Kojić, Milan and Filipović, Nenad and Stevanović, Magdalena and Milenković, Marina",
year = "2022",
abstract = "Aims: To investigate the synergistic activity of colistin and selenium nanoparticles (SeNPs) against pandrug-resistant (PDR) Ac. baumannii. Methods and Results: Chequerboard and time-kill assays were employed to ex- plore the potential synergistic interactions between colistin and SeNPs against Ac. baumannii isolates (8), previously determined as colistin-resistant (MIC range 16– 256 μg ml−1 ). Also, whole-genome sequencing (WGS) and gene expression analyses were used to elucidate the mechanisms of colistin resistance. Exceptionally strong synergistic activity (FICI range 0.004–0.035) of colistin and SeNPs against colistin- resistant isolates was revealed. Colistin (0.5 or 1 μg ml −1 ) used in combination with SeNPs (0.5 μg ml−1 ) was able to reduce initial inoculum during the first 4 h of incuba- tion, in contrast to colistin (0.5, 1 or 2 μg ml−1 ) alone. Conclusions: These findings propose colistin/SeNPs combination as a new option to fight PDR Ac. baumannii, the therapeutic possibilities of which should be proved in future in vivo studies. Significance and Impact of Study: Here we present the first evidence of synergy between colistin and selenium compounds against bacteria in general. Also, WGS and gene expression analyses provide some new insights into Ac. baumannii colistin resistance mechanisms.",
publisher = "John Wiley and Sons Inc",
journal = "Journal of Applied Microbiology",
title = "In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles",
pages = "1197-1206",
volume = "133",
number = "3",
doi = "10.1111/jam.15638",
url = "https://hdl.handle.net/21.15107/rcub_dais_13449"
}

Ušjak, D., Novović, K., Filipić, B., Kojić, M., Filipović, N., Stevanović, M.,& Milenković, M.. (2022). In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles. in Journal of Applied Microbiology
John Wiley and Sons Inc., 133(3), 1197-1206.
https://doi.org/10.1111/jam.15638
https://hdl.handle.net/21.15107/rcub_dais_13449

Ušjak D, Novović K, Filipić B, Kojić M, Filipović N, Stevanović M, Milenković M. In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles. in Journal of Applied Microbiology. 2022;133(3):1197-1206.
doi:10.1111/jam.15638
https://hdl.handle.net/21.15107/rcub_dais_13449 .

Ušjak, Dušan, Novović, Katarina, Filipić, Brankica, Kojić, Milan, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina, "In vitro colistin susceptibility of pandrug-resistant Ac. baumannii is restored in the presence of selenium nanoparticles" in Journal of Applied Microbiology, 133, no. 3 (2022):1197-1206,
https://doi.org/10.1111/jam.15638 .,
https://hdl.handle.net/21.15107/rcub_dais_13449 .

TY  - JOUR
AU  - Ušjak, Dušan
AU  - Dinić, Miroslav
AU  - Novović, Katarina
AU  - Ivković, Branka
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
AU  - Milenković, Marina T.
PY  - 2021
UR  - https://dais.sanu.ac.rs/123456789/10034
AB  - An increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real‐time PCR was used to evaluate mRNA expression of biofilm‐associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin‐ and collagen‐mediated adhesion, surface motility, and quorum‐sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2′‐hydroxy‐2‐methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.
PB  - Wiley
T2  - Chemistry & Biodiversity
T1  - Methoxy‐Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of                    Acinetobacter baumannii                    by Inhibiting                    ompA                    Gene Expression
SP  - e2000786
VL  - 18
IS  - 1
DO  - 10.1002/cbdv.202000786
UR  - https://hdl.handle.net/21.15107/rcub_dais_10034
ER  - 

@article{
author = "Ušjak, Dušan and Dinić, Miroslav and Novović, Katarina and Ivković, Branka and Filipović, Nenad and Stevanović, Magdalena and Milenković, Marina T.",
year = "2021",
abstract = "An increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real‐time PCR was used to evaluate mRNA expression of biofilm‐associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin‐ and collagen‐mediated adhesion, surface motility, and quorum‐sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2′‐hydroxy‐2‐methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.",
publisher = "Wiley",
journal = "Chemistry & Biodiversity",
title = "Methoxy‐Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of                    Acinetobacter baumannii                    by Inhibiting                    ompA                    Gene Expression",
pages = "e2000786",
volume = "18",
number = "1",
doi = "10.1002/cbdv.202000786",
url = "https://hdl.handle.net/21.15107/rcub_dais_10034"
}

Ušjak, D., Dinić, M., Novović, K., Ivković, B., Filipović, N., Stevanović, M.,& Milenković, M. T.. (2021). Methoxy‐Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of                    Acinetobacter baumannii                    by Inhibiting                    ompA                    Gene Expression. in Chemistry & Biodiversity
Wiley., 18(1), e2000786.
https://doi.org/10.1002/cbdv.202000786
https://hdl.handle.net/21.15107/rcub_dais_10034

Ušjak D, Dinić M, Novović K, Ivković B, Filipović N, Stevanović M, Milenković MT. Methoxy‐Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of                    Acinetobacter baumannii                    by Inhibiting                    ompA                    Gene Expression. in Chemistry & Biodiversity. 2021;18(1):e2000786.
doi:10.1002/cbdv.202000786
https://hdl.handle.net/21.15107/rcub_dais_10034 .

Ušjak, Dušan, Dinić, Miroslav, Novović, Katarina, Ivković, Branka, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina T., "Methoxy‐Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of                    Acinetobacter baumannii                    by Inhibiting                    ompA                    Gene Expression" in Chemistry & Biodiversity, 18, no. 1 (2021):e2000786,
https://doi.org/10.1002/cbdv.202000786 .,
https://hdl.handle.net/21.15107/rcub_dais_10034 .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Ušjak, Dušan
AU  - Milenković, Marina
AU  - Zheng, Kai
AU  - Liverani, Liliana
AU  - Boccaccini, Aldo
AU  - Stevanović, Magdalena
PY  - 2021
UR  - https://dais.sanu.ac.rs/123456789/11631
AB  - Although selenium nanoparticles (SeNPs) have gained attention in the scientific community mostly through investigation of their anticancer activity, a great potential of this nanomaterial was recognized recently regarding its antimicrobial activity. The particle form, size, and surface chemistry have been recognized as crucial parameters determining the interaction of nanomaterials with biological entities. Furthermore, considering a narrow boundary between beneficial and toxic effects for selenium per se, it is clear that investigations of biomedical applications of SeNPs are very demanding and must be done with great precautions. The goal of this work is to evaluate the effects of SeNPs surface chemistry and structure on antimicrobial activity against several common bacterial strains, including Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 6633), and Kocuria rhizophila (ATCC 9341), as well as Escherichia coli (ATCC 8739), Salmonella Abony (NCTC 6017), Klebsiella pneumoniae (NCIMB 9111) and Pseudomonas aeruginosa (ATCC 9027), and the standard yeast strain Candida albicans (ATCC 10231). Three types of SeNPs were synthesized by chemical reduction approach using different stabilizers and reducing agents: (i) bovine serum albumin (BSA) + ascorbic acid, (ii) chitosan + ascorbic acid, and (iii) with glucose. A thorough physicochemical characterization of the obtained SeNPs was performed to determine the effects of varying synthesis parameters on their morphology, size, structure, and surface chemistry. All SeNPs were amorphous, with spherical morphology and size in the range 70–300 nm. However, the SeNPs obtained under different synthesis conditions, i.e. by using different stabilizers as well as reducing agents, exhibited different antimicrobial activity as well as cytotoxicity which are crucial for their applications. In this paper, the antimicrobial screening of the selected systems is presented, which was determined by the broth microdilution method, and inhibitory influence on the production of monomicrobial and dual-species biofilm was evaluated. The potential mechanism of action of different systems is proposed. Additionally, the cytotoxicity of SeNPs was examined on the MRC-5 cell line, in the same concentration interval as for antimicrobial testing. It was shown that formulation SeNPs-BSA expressed a significantly lower cytotoxic effect than the other two formulations.
PB  - Frontiers Media SA
T2  - Frontiers in Bioengineering and Biotechnology
T1  - Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure
VL  - 8
DO  - 10.3389/fbioe.2020.624621
UR  - https://hdl.handle.net/21.15107/rcub_dais_11631
ER  - 

@article{
author = "Filipović, Nenad and Ušjak, Dušan and Milenković, Marina and Zheng, Kai and Liverani, Liliana and Boccaccini, Aldo and Stevanović, Magdalena",
year = "2021",
abstract = "Although selenium nanoparticles (SeNPs) have gained attention in the scientific community mostly through investigation of their anticancer activity, a great potential of this nanomaterial was recognized recently regarding its antimicrobial activity. The particle form, size, and surface chemistry have been recognized as crucial parameters determining the interaction of nanomaterials with biological entities. Furthermore, considering a narrow boundary between beneficial and toxic effects for selenium per se, it is clear that investigations of biomedical applications of SeNPs are very demanding and must be done with great precautions. The goal of this work is to evaluate the effects of SeNPs surface chemistry and structure on antimicrobial activity against several common bacterial strains, including Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 6633), and Kocuria rhizophila (ATCC 9341), as well as Escherichia coli (ATCC 8739), Salmonella Abony (NCTC 6017), Klebsiella pneumoniae (NCIMB 9111) and Pseudomonas aeruginosa (ATCC 9027), and the standard yeast strain Candida albicans (ATCC 10231). Three types of SeNPs were synthesized by chemical reduction approach using different stabilizers and reducing agents: (i) bovine serum albumin (BSA) + ascorbic acid, (ii) chitosan + ascorbic acid, and (iii) with glucose. A thorough physicochemical characterization of the obtained SeNPs was performed to determine the effects of varying synthesis parameters on their morphology, size, structure, and surface chemistry. All SeNPs were amorphous, with spherical morphology and size in the range 70–300 nm. However, the SeNPs obtained under different synthesis conditions, i.e. by using different stabilizers as well as reducing agents, exhibited different antimicrobial activity as well as cytotoxicity which are crucial for their applications. In this paper, the antimicrobial screening of the selected systems is presented, which was determined by the broth microdilution method, and inhibitory influence on the production of monomicrobial and dual-species biofilm was evaluated. The potential mechanism of action of different systems is proposed. Additionally, the cytotoxicity of SeNPs was examined on the MRC-5 cell line, in the same concentration interval as for antimicrobial testing. It was shown that formulation SeNPs-BSA expressed a significantly lower cytotoxic effect than the other two formulations.",
publisher = "Frontiers Media SA",
journal = "Frontiers in Bioengineering and Biotechnology",
title = "Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure",
volume = "8",
doi = "10.3389/fbioe.2020.624621",
url = "https://hdl.handle.net/21.15107/rcub_dais_11631"
}

Filipović, N., Ušjak, D., Milenković, M., Zheng, K., Liverani, L., Boccaccini, A.,& Stevanović, M.. (2021). Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure. in Frontiers in Bioengineering and Biotechnology
Frontiers Media SA., 8.
https://doi.org/10.3389/fbioe.2020.624621
https://hdl.handle.net/21.15107/rcub_dais_11631

Filipović N, Ušjak D, Milenković M, Zheng K, Liverani L, Boccaccini A, Stevanović M. Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure. in Frontiers in Bioengineering and Biotechnology. 2021;8.
doi:10.3389/fbioe.2020.624621
https://hdl.handle.net/21.15107/rcub_dais_11631 .

Filipović, Nenad, Ušjak, Dušan, Milenković, Marina, Zheng, Kai, Liverani, Liliana, Boccaccini, Aldo, Stevanović, Magdalena, "Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure" in Frontiers in Bioengineering and Biotechnology, 8 (2021),
https://doi.org/10.3389/fbioe.2020.624621 .,
https://hdl.handle.net/21.15107/rcub_dais_11631 .

TY  - JOUR
AU  - Ušjak, Dušan
AU  - Dinić, Miroslav
AU  - Novović, Katarina
AU  - Ivković, Branka
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
AU  - Milenković, Marina
PY  - 2021
UR  - https://dais.sanu.ac.rs/123456789/11878
AB  - An increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real-time PCR was used to evaluate mRNA expression of biofilm-associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin- and collagen-mediated adhesion, surface motility, and quorum-sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2′-hydroxy-2-methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.
PB  - Wiley-VCH
T2  - Chemistry and Biodiversity
T1  - Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,Adhesion and Surface Motility of Acinetobacter baumannii byInhibiting ompA Gene Expression
SP  - e2000786
VL  - 18
IS  - 1
DO  - 10.1002/cbdv.202000786
UR  - https://hdl.handle.net/21.15107/rcub_dais_11878
ER  - 

@article{
author = "Ušjak, Dušan and Dinić, Miroslav and Novović, Katarina and Ivković, Branka and Filipović, Nenad and Stevanović, Magdalena and Milenković, Marina",
year = "2021",
abstract = "An increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real-time PCR was used to evaluate mRNA expression of biofilm-associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin- and collagen-mediated adhesion, surface motility, and quorum-sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2′-hydroxy-2-methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.",
publisher = "Wiley-VCH",
journal = "Chemistry and Biodiversity",
title = "Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,Adhesion and Surface Motility of Acinetobacter baumannii byInhibiting ompA Gene Expression",
pages = "e2000786",
volume = "18",
number = "1",
doi = "10.1002/cbdv.202000786",
url = "https://hdl.handle.net/21.15107/rcub_dais_11878"
}

Ušjak, D., Dinić, M., Novović, K., Ivković, B., Filipović, N., Stevanović, M.,& Milenković, M.. (2021). Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,Adhesion and Surface Motility of Acinetobacter baumannii byInhibiting ompA Gene Expression. in Chemistry and Biodiversity
Wiley-VCH., 18(1), e2000786.
https://doi.org/10.1002/cbdv.202000786
https://hdl.handle.net/21.15107/rcub_dais_11878

Ušjak D, Dinić M, Novović K, Ivković B, Filipović N, Stevanović M, Milenković M. Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,Adhesion and Surface Motility of Acinetobacter baumannii byInhibiting ompA Gene Expression. in Chemistry and Biodiversity. 2021;18(1):e2000786.
doi:10.1002/cbdv.202000786
https://hdl.handle.net/21.15107/rcub_dais_11878 .

Ušjak, Dušan, Dinić, Miroslav, Novović, Katarina, Ivković, Branka, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina, "Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production,Adhesion and Surface Motility of Acinetobacter baumannii byInhibiting ompA Gene Expression" in Chemistry and Biodiversity, 18, no. 1 (2021):e2000786,
https://doi.org/10.1002/cbdv.202000786 .,
https://hdl.handle.net/21.15107/rcub_dais_11878 .

TY  - CONF
AU  - Ušjak, Dušan
AU  - Dinić, Miroslav
AU  - Novović, Katarina
AU  - Ivković, Branka
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
AU  - Milenković, Marina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3758
UR  - https://dais.sanu.ac.rs/123456789/10086
AB  - Acinetobacter baumannii je globalno rasprostranjen nozokomijalni patogen koji se odlikuje izuzetnom sposobnošću ekstremno brzog sticanja rezistencije na antibiotike, kao i adaptacije na preživljavanje u suvim uslovima bolničke sredine [1]. Zbog velike zastupljenosti rezistentnih sojeva protiv kojih ne postoji delotvorna terapija, Svetska zdravstvena organizacija (WHO, 2017) i Centri za kontrolu i prevenciju bolesti (CDC, 2019), označili su A. baumannii kao patogen od kritične važnosti za otkriće novih antimikrobnih agenasa ili novih terapijskih strategija [2]. Targetiranje virulencije je oblik alternativnog terapijskog pristupa koji pruža mogućnost prevencije teže kliničke slike kod inficiranih pacijenata posredstvom inhibicije ekspresije ključnih faktora virulencije, uz istovremenu redukovanu selekciju rezistentnih mutanata [3].Rezultati i Diskusija: Od četiri različito supstituisana hidroksihalkona, sintetisanih u postupku bazno-katalizovane Claisen-Schmidt kondenzacije, selektiran je metkosi-supstituisani derivat kao najpotentniji inhibitor produkcije biofilma kod A. baumannii. Primenom Real-Time kvantitativne PCR metode sa reverznom transkriptazom ispitan je uticaj subinhibitornih koncentracija selektiranog jedinjenja (70, 35 i 10 μg/mL) na ekspresiju gena faktora virulencije povezanih sa produkcijom biofilma kod A. baumannii: ompA, bap i abaI. Pokazana je značajna dozno-zavisna nishodna ekspresija ompA gena, koji kodira OmpA protein spoljašnje membrane ćelijskog zida, koji učestvuje u brojnim virulentnim osobinama A. baumannii, kao što su adhezija, citotoksičnost, motilitet i rezistencija na imunski odgovor i antibiotike [4]. Takođe, zabeležena je značajna inhibicija ekspresije bap gena, koja je neophodna za adheziju na humane epitelne ćelije, i abaI gena, integralnog dela bakterijskog kvorum-sensing sistema, koji kodira sintazu autoinduktorskih molekula. Sposobnost antivirulentnog delovanja metoksi-supstituisanog derivata hidroksihalkona potvrđena je demonstracijom inhibicije fenotipske ekspresije faktora virulencije povezanih sa ekspresijom ompA, bap i abaI gena, kao što su adhezija za komponente ekstracelularnog matriksa (fibronektin i kolagen), površinski motilitet i produkcija autoinduktorskih molekula.Zaključak: Metoksi-supstituisani hidroksihalkon ispoljava antivirulentno dejstvo protiv A. baumannii, pre svega posredstvom nishodne regulacije ompA gena, što se reflektuje u inhibiciji produkcije biofilma, sposobnosti adhezije i površinskog motiliteta ovog patogena.
AB  - Over the last two decades, Acinetobacter baumannii has emerged as one of the most troublesome pathogens, rapidly acquiring resistance to virtually all available antibiotics. This has urged researchers to seek alternative ways to fight this pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm activity of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. We used quantitative Real-Time PCR to evaluate mRNA expression of virulence-associated genes (ompA, bap, abaI) in extensively drug-resistant (XDR) A. baumannii wound isolate and A. baumannii ATCC 19606 strain, treated with selected compound. Also, we tested biofilm production, fibronectin- and collagen-mediated adhesion, surface motility and quorum-sensing activity of treated strains. The results revealed downregulation of the expression of all tested virulence genes together with the reduction of biofilm production, adhesion and motility. The most notable finding is significant reduction of ompA gene expression, whose encoded protein product is associated with numerous virulence traits of A. baumannii. Therefore, we conclude that selected methoxy-substituted hydroxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of the bacterial adhesins, most importantly OmpA, which is reflected in reduced biofilm formation, adhesion and surface motility.
C3  - FEMS Online Conference on Microbiology
T1  - Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression
UR  - https://hdl.handle.net/21.15107/rcub_dais_10086
ER  - 

@conference{
author = "Ušjak, Dušan and Dinić, Miroslav and Novović, Katarina and Ivković, Branka and Filipović, Nenad and Stevanović, Magdalena and Milenković, Marina",
year = "2020",
abstract = "Acinetobacter baumannii je globalno rasprostranjen nozokomijalni patogen koji se odlikuje izuzetnom sposobnošću ekstremno brzog sticanja rezistencije na antibiotike, kao i adaptacije na preživljavanje u suvim uslovima bolničke sredine [1]. Zbog velike zastupljenosti rezistentnih sojeva protiv kojih ne postoji delotvorna terapija, Svetska zdravstvena organizacija (WHO, 2017) i Centri za kontrolu i prevenciju bolesti (CDC, 2019), označili su A. baumannii kao patogen od kritične važnosti za otkriće novih antimikrobnih agenasa ili novih terapijskih strategija [2]. Targetiranje virulencije je oblik alternativnog terapijskog pristupa koji pruža mogućnost prevencije teže kliničke slike kod inficiranih pacijenata posredstvom inhibicije ekspresije ključnih faktora virulencije, uz istovremenu redukovanu selekciju rezistentnih mutanata [3].Rezultati i Diskusija: Od četiri različito supstituisana hidroksihalkona, sintetisanih u postupku bazno-katalizovane Claisen-Schmidt kondenzacije, selektiran je metkosi-supstituisani derivat kao najpotentniji inhibitor produkcije biofilma kod A. baumannii. Primenom Real-Time kvantitativne PCR metode sa reverznom transkriptazom ispitan je uticaj subinhibitornih koncentracija selektiranog jedinjenja (70, 35 i 10 μg/mL) na ekspresiju gena faktora virulencije povezanih sa produkcijom biofilma kod A. baumannii: ompA, bap i abaI. Pokazana je značajna dozno-zavisna nishodna ekspresija ompA gena, koji kodira OmpA protein spoljašnje membrane ćelijskog zida, koji učestvuje u brojnim virulentnim osobinama A. baumannii, kao što su adhezija, citotoksičnost, motilitet i rezistencija na imunski odgovor i antibiotike [4]. Takođe, zabeležena je značajna inhibicija ekspresije bap gena, koja je neophodna za adheziju na humane epitelne ćelije, i abaI gena, integralnog dela bakterijskog kvorum-sensing sistema, koji kodira sintazu autoinduktorskih molekula. Sposobnost antivirulentnog delovanja metoksi-supstituisanog derivata hidroksihalkona potvrđena je demonstracijom inhibicije fenotipske ekspresije faktora virulencije povezanih sa ekspresijom ompA, bap i abaI gena, kao što su adhezija za komponente ekstracelularnog matriksa (fibronektin i kolagen), površinski motilitet i produkcija autoinduktorskih molekula.Zaključak: Metoksi-supstituisani hidroksihalkon ispoljava antivirulentno dejstvo protiv A. baumannii, pre svega posredstvom nishodne regulacije ompA gena, što se reflektuje u inhibiciji produkcije biofilma, sposobnosti adhezije i površinskog motiliteta ovog patogena., Over the last two decades, Acinetobacter baumannii has emerged as one of the most troublesome pathogens, rapidly acquiring resistance to virtually all available antibiotics. This has urged researchers to seek alternative ways to fight this pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm activity of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. We used quantitative Real-Time PCR to evaluate mRNA expression of virulence-associated genes (ompA, bap, abaI) in extensively drug-resistant (XDR) A. baumannii wound isolate and A. baumannii ATCC 19606 strain, treated with selected compound. Also, we tested biofilm production, fibronectin- and collagen-mediated adhesion, surface motility and quorum-sensing activity of treated strains. The results revealed downregulation of the expression of all tested virulence genes together with the reduction of biofilm production, adhesion and motility. The most notable finding is significant reduction of ompA gene expression, whose encoded protein product is associated with numerous virulence traits of A. baumannii. Therefore, we conclude that selected methoxy-substituted hydroxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of the bacterial adhesins, most importantly OmpA, which is reflected in reduced biofilm formation, adhesion and surface motility.",
journal = "FEMS Online Conference on Microbiology",
title = "Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression",
url = "https://hdl.handle.net/21.15107/rcub_dais_10086"
}

Ušjak, D., Dinić, M., Novović, K., Ivković, B., Filipović, N., Stevanović, M.,& Milenković, M.. (2020). Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression. in FEMS Online Conference on Microbiology.
https://hdl.handle.net/21.15107/rcub_dais_10086

Ušjak D, Dinić M, Novović K, Ivković B, Filipović N, Stevanović M, Milenković M. Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression. in FEMS Online Conference on Microbiology. 2020;.
https://hdl.handle.net/21.15107/rcub_dais_10086 .

Ušjak, Dušan, Dinić, Miroslav, Novović, Katarina, Ivković, Branka, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina, "Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression" in FEMS Online Conference on Microbiology (2020),
https://hdl.handle.net/21.15107/rcub_dais_10086 .