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Ušjak, Dušan

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  • Ušjak, Dušan (2)
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Methoxy-substituted hydroxychalcone reduces biofilm production, adhesion, and surface motility of Acinetobacter baumannii by inhibiting ompA gene expression

Ušjak, Dušan; Dinić, Miroslav; Novović, Katarina; Ivković, Branka; Filipović, Nenad; Stevanović, Magdalena; Milenković, Marina

(2020)

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
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",
url = "https://farfar.pharmacy.bg.ac.rs/handle/123456789/3758, https://dais.sanu.ac.rs/123456789/10086",
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"
}
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.
FEMS Online Conference on Microbiology, null. 
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. FEMS Online Conference on Microbiology. 2020;

Methoxy‐Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of Acinetobacter baumannii by Inhibiting ompA Gene Expression

Ušjak, Dušan; Dinić, Miroslav; Novović, Katarina; Ivković, Branka; Filipović, Nenad; Stevanović, Magdalena; Milenković, Marina T.

(Wiley, 2020)

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  - 2020
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
DO  - 10.1002/cbdv.202000786
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 = "2020",
url = "https://dais.sanu.ac.rs/123456789/10034",
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",
doi = "10.1002/cbdv.202000786"
}
Ušjak, D., Dinić, M., Novović, K., Ivković, B., Filipović, N., Stevanović, M.,& Milenković, M. T. (2020). Methoxy‐Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of                    Acinetobacter baumannii                    by Inhibiting                    ompA                    Gene Expression.
Chemistry & BiodiversityWiley., null. 
https://doi.org/10.1002/cbdv.202000786
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. Chemistry & Biodiversity. 2020;
3