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  - DATA
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/123456789/11879
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 Verlag
T2  - Chemistry and Biodiversity
T1  - Supporting information for 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
VL  - 18
IS  - 1
UR  - https://hdl.handle.net/21.15107/rcub_dais_11879
ER  - 

@misc{
author = "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 Verlag",
journal = "Chemistry and Biodiversity",
title = "Supporting information for 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",
volume = "18",
number = "1",
url = "https://hdl.handle.net/21.15107/rcub_dais_11879"
}

Dinić, M., Novović, K., Ivković, B., Filipović, N., Stevanović, M.,& Milenković, M.. (2021). Supporting information for 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. in Chemistry and Biodiversity
Wiley-VCH Verlag., 18(1).
https://hdl.handle.net/21.15107/rcub_dais_11879

Dinić M, Novović K, Ivković B, Filipović N, Stevanović M, Milenković M. Supporting information for 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. in Chemistry and Biodiversity. 2021;18(1).
https://hdl.handle.net/21.15107/rcub_dais_11879 .

Dinić, Miroslav, Novović, Katarina, Ivković, Branka, Filipović, Nenad, Stevanović, Magdalena, Milenković, Marina, "Supporting information for 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" in Chemistry and Biodiversity, 18, no. 1 (2021),
https://hdl.handle.net/21.15107/rcub_dais_11879 .

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  - JOUR
AU  - Brdarić, Emilija
AU  - Soković Bajić, Svetlana
AU  - Đokić, Jelena
AU  - Đurđić, Slađana
AU  - Ruas-Madiedo, Patricia
AU  - Stevanović, Magdalena
AU  - Tolinački, Maja
AU  - Dinić, Miroslav
AU  - Mutić, Jelena
AU  - Golić, Nataša
AU  - Živković, Milica
PY  - 2021
UR  - https://dais.sanu.ac.rs/123456789/12357
AB  - Cadmium (Cd) ranks seventh on the list of most significant potential threats to human health based on its suspected toxicity and the possibility of exposure to it. It has been reported that some bacterial exopolysaccharides (EPSs) have the ability to bind heavy metal ions. We therefore investigated the capacity of eight EPS-producing lactobacilli to adsorb Cd in the present study, and Lactiplantibacillus plantarum BGAN8 was chosen as the best candidate. In addition, we demonstrate that an EPS derived from BGAN8 (EPS-AN8) exhibits a high Cd-binding capacity and prevents Cd-mediated toxicity in intestinal epithelial Caco-2 cells. Simultaneous use of EPS-AN8 with Cd treatment prevents inflammation, disruption of tight-junction proteins, and oxidative stress. Our results indicate that the EPS in question has a strong potential to be used as a postbiotic in combatting the adverse effects of Cd. Moreover, we show that higher concentrations of EPS-AN8 can alleviate Cd-induced cell damage.
PB  - Frontiers
T2  - Frontiers in Microbiology
T1  - Protective Effect of an Exopolysaccharide Produced by Lactiplantibacillus plantarum BGAN8 Against Cadmium-Induced Toxicity in Caco-2 Cells
SP  - 3222
VL  - 12
DO  - 10.3389/fmicb.2021.759378
UR  - https://hdl.handle.net/21.15107/rcub_dais_12357
ER  - 

@article{
author = "Brdarić, Emilija and Soković Bajić, Svetlana and Đokić, Jelena and Đurđić, Slađana and Ruas-Madiedo, Patricia and Stevanović, Magdalena and Tolinački, Maja and Dinić, Miroslav and Mutić, Jelena and Golić, Nataša and Živković, Milica",
year = "2021",
abstract = "Cadmium (Cd) ranks seventh on the list of most significant potential threats to human health based on its suspected toxicity and the possibility of exposure to it. It has been reported that some bacterial exopolysaccharides (EPSs) have the ability to bind heavy metal ions. We therefore investigated the capacity of eight EPS-producing lactobacilli to adsorb Cd in the present study, and Lactiplantibacillus plantarum BGAN8 was chosen as the best candidate. In addition, we demonstrate that an EPS derived from BGAN8 (EPS-AN8) exhibits a high Cd-binding capacity and prevents Cd-mediated toxicity in intestinal epithelial Caco-2 cells. Simultaneous use of EPS-AN8 with Cd treatment prevents inflammation, disruption of tight-junction proteins, and oxidative stress. Our results indicate that the EPS in question has a strong potential to be used as a postbiotic in combatting the adverse effects of Cd. Moreover, we show that higher concentrations of EPS-AN8 can alleviate Cd-induced cell damage.",
publisher = "Frontiers",
journal = "Frontiers in Microbiology",
title = "Protective Effect of an Exopolysaccharide Produced by Lactiplantibacillus plantarum BGAN8 Against Cadmium-Induced Toxicity in Caco-2 Cells",
pages = "3222",
volume = "12",
doi = "10.3389/fmicb.2021.759378",
url = "https://hdl.handle.net/21.15107/rcub_dais_12357"
}

Brdarić, E., Soković Bajić, S., Đokić, J., Đurđić, S., Ruas-Madiedo, P., Stevanović, M., Tolinački, M., Dinić, M., Mutić, J., Golić, N.,& Živković, M.. (2021). Protective Effect of an Exopolysaccharide Produced by Lactiplantibacillus plantarum BGAN8 Against Cadmium-Induced Toxicity in Caco-2 Cells. in Frontiers in Microbiology
Frontiers., 12, 3222.
https://doi.org/10.3389/fmicb.2021.759378
https://hdl.handle.net/21.15107/rcub_dais_12357

Brdarić E, Soković Bajić S, Đokić J, Đurđić S, Ruas-Madiedo P, Stevanović M, Tolinački M, Dinić M, Mutić J, Golić N, Živković M. Protective Effect of an Exopolysaccharide Produced by Lactiplantibacillus plantarum BGAN8 Against Cadmium-Induced Toxicity in Caco-2 Cells. in Frontiers in Microbiology. 2021;12:3222.
doi:10.3389/fmicb.2021.759378
https://hdl.handle.net/21.15107/rcub_dais_12357 .

Brdarić, Emilija, Soković Bajić, Svetlana, Đokić, Jelena, Đurđić, Slađana, Ruas-Madiedo, Patricia, Stevanović, Magdalena, Tolinački, Maja, Dinić, Miroslav, Mutić, Jelena, Golić, Nataša, Živković, Milica, "Protective Effect of an Exopolysaccharide Produced by Lactiplantibacillus plantarum BGAN8 Against Cadmium-Induced Toxicity in Caco-2 Cells" in Frontiers in Microbiology, 12 (2021):3222,
https://doi.org/10.3389/fmicb.2021.759378 .,
https://hdl.handle.net/21.15107/rcub_dais_12357 .

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 .

TY  - JOUR
AU  - Dinić, Miroslav
AU  - Pecikoza, Uroš
AU  - Đokić, Jelena
AU  - Stepanović Petrović, Radica
AU  - Milenković, Marina
AU  - Stevanović, Magdalena
AU  - Filipović, Nenad
AU  - Begović, Jelena
AU  - Golić, Nataša
AU  - Lukić, Jovanka
PY  - 2018
UR  - https://dais.sanu.ac.rs/123456789/2347
AB  - The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS) produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11) to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR) and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia) and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1β and iNOS mRNAs in rat’s paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1β, TNF-α and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.
PB  - Lausanne : Frontiers
T2  - Frontiers in Pharmacology
T1  - Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats
SP  - Article 1
VL  - 9
DO  - 10.3389/fphar.2018.00001
UR  - https://hdl.handle.net/21.15107/rcub_dais_2347
ER  - 

@article{
author = "Dinić, Miroslav and Pecikoza, Uroš and Đokić, Jelena and Stepanović Petrović, Radica and Milenković, Marina and Stevanović, Magdalena and Filipović, Nenad and Begović, Jelena and Golić, Nataša and Lukić, Jovanka",
year = "2018",
abstract = "The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS) produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11) to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR) and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia) and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1β and iNOS mRNAs in rat’s paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1β, TNF-α and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.",
publisher = "Lausanne : Frontiers",
journal = "Frontiers in Pharmacology",
title = "Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats",
pages = "Article 1",
volume = "9",
doi = "10.3389/fphar.2018.00001",
url = "https://hdl.handle.net/21.15107/rcub_dais_2347"
}

Dinić, M., Pecikoza, U., Đokić, J., Stepanović Petrović, R., Milenković, M., Stevanović, M., Filipović, N., Begović, J., Golić, N.,& Lukić, J.. (2018). Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats. in Frontiers in Pharmacology
Lausanne : Frontiers., 9, Article 1.
https://doi.org/10.3389/fphar.2018.00001
https://hdl.handle.net/21.15107/rcub_dais_2347

Dinić M, Pecikoza U, Đokić J, Stepanović Petrović R, Milenković M, Stevanović M, Filipović N, Begović J, Golić N, Lukić J. Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats. in Frontiers in Pharmacology. 2018;9:Article 1.
doi:10.3389/fphar.2018.00001
https://hdl.handle.net/21.15107/rcub_dais_2347 .

Dinić, Miroslav, Pecikoza, Uroš, Đokić, Jelena, Stepanović Petrović, Radica, Milenković, Marina, Stevanović, Magdalena, Filipović, Nenad, Begović, Jelena, Golić, Nataša, Lukić, Jovanka, "Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats" in Frontiers in Pharmacology, 9 (2018):Article 1,
https://doi.org/10.3389/fphar.2018.00001 .,
https://hdl.handle.net/21.15107/rcub_dais_2347 .