TY  - JOUR
AU  - Djokic, Lidija
AU  - Stankovic, Nada
AU  - Galic, Ivana
AU  - Moric, Ivana
AU  - Radakovic, Natasa
AU  - Šegan, Sandra
AU  - Pavic, Aleksandar
AU  - Senerovic, Lidija
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5579
AB  - Bacterial infections have become increasingly difficult to treat due to the occurrence of antibiotic-resistant strains. A promising strategy to increase the efficacy of therapy is to combine antibacterials with agents that decrease pathogen virulence via the modulation of the quorum sensing (QS). Lactonases inhibit acylated homoserine lactone (AHL)-mediated QS in Gram-negative bacteria, including the leading nosocomial pathogen Pseudomonas aeruginosa. Here we describe the characteristics of heterologously expressed YtnP lactonase from Bacillus paralicheniformis ZP1 (YtnP-ZP1) isolated from agricultural soil using the culture enrichment method. Purified YtnP-ZP1 hydrolyzed different AHLs with preference to substrates with long acyl residues as evaluated in assays with biosensors and HPLC. The enzyme showed good thermostability and activity in a wide temperature range. YtnP-ZP1 in 50 μg mL–1 concentration reduced the amount of P. aeruginosa-produced long-chain AHLs by 85%, while it hydrolyzed 50% of short-chain AHLs. Incubation of P. aeruginosa PAO1 with YtnP-ZP1 reduced its swarming motility and elastolytic activity without bactericidal effect. YtnP-ZP1 caused the inhibition of biofilm formation and disintegration of mature biofilms in P. aeruginosa PAO1 and multiresistant clinical strain BR5H that was visualized by crystal violet staining. The treatment with YtnP-ZP1 in concentrations higher than 25 μg mL–1 improved the survival of P. aeruginosa PAO1-infected zebrafish (Danio rerio), rescuing 80% of embryos, while in combination with tobramycin or gentamicin survival rate increased to 100%. The treatment of P. aeruginosa PAO1 biofilms on infected zebrafish tail wounds with 50 μg mL–1 YtnP-ZP1 and 2 × MIC tobramycin led to infection clearing in 2 days. The extensive toxicity studies proved YtnP-ZP1 was non-toxic to human cells and zebrafish. In conclusion, novel YtnP-ZP1 lactonase with its effective anti-virulence activity could be used to increase the efficacy of clinically approved antibiotics in clearing both systemic and biofilm-associated P. aeruginosa infections.
PB  - Frontiers Media SA
T2  - Frontiers in Microbiology
T1  - Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo
VL  - 13
SP  - 906312
DO  - 10.3389/fmicb.2022.906312
ER  - 

@article{
author = "Djokic, Lidija and Stankovic, Nada and Galic, Ivana and Moric, Ivana and Radakovic, Natasa and Šegan, Sandra and Pavic, Aleksandar and Senerovic, Lidija",
year = "2022",
abstract = "Bacterial infections have become increasingly difficult to treat due to the occurrence of antibiotic-resistant strains. A promising strategy to increase the efficacy of therapy is to combine antibacterials with agents that decrease pathogen virulence via the modulation of the quorum sensing (QS). Lactonases inhibit acylated homoserine lactone (AHL)-mediated QS in Gram-negative bacteria, including the leading nosocomial pathogen Pseudomonas aeruginosa. Here we describe the characteristics of heterologously expressed YtnP lactonase from Bacillus paralicheniformis ZP1 (YtnP-ZP1) isolated from agricultural soil using the culture enrichment method. Purified YtnP-ZP1 hydrolyzed different AHLs with preference to substrates with long acyl residues as evaluated in assays with biosensors and HPLC. The enzyme showed good thermostability and activity in a wide temperature range. YtnP-ZP1 in 50 μg mL–1 concentration reduced the amount of P. aeruginosa-produced long-chain AHLs by 85%, while it hydrolyzed 50% of short-chain AHLs. Incubation of P. aeruginosa PAO1 with YtnP-ZP1 reduced its swarming motility and elastolytic activity without bactericidal effect. YtnP-ZP1 caused the inhibition of biofilm formation and disintegration of mature biofilms in P. aeruginosa PAO1 and multiresistant clinical strain BR5H that was visualized by crystal violet staining. The treatment with YtnP-ZP1 in concentrations higher than 25 μg mL–1 improved the survival of P. aeruginosa PAO1-infected zebrafish (Danio rerio), rescuing 80% of embryos, while in combination with tobramycin or gentamicin survival rate increased to 100%. The treatment of P. aeruginosa PAO1 biofilms on infected zebrafish tail wounds with 50 μg mL–1 YtnP-ZP1 and 2 × MIC tobramycin led to infection clearing in 2 days. The extensive toxicity studies proved YtnP-ZP1 was non-toxic to human cells and zebrafish. In conclusion, novel YtnP-ZP1 lactonase with its effective anti-virulence activity could be used to increase the efficacy of clinically approved antibiotics in clearing both systemic and biofilm-associated P. aeruginosa infections.",
publisher = "Frontiers Media SA",
journal = "Frontiers in Microbiology",
title = "Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo",
volume = "13",
pages = "906312",
doi = "10.3389/fmicb.2022.906312"
}

Djokic, L., Stankovic, N., Galic, I., Moric, I., Radakovic, N., Šegan, S., Pavic, A.,& Senerovic, L.. (2022). Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo. in Frontiers in Microbiology
Frontiers Media SA., 13, 906312.
https://doi.org/10.3389/fmicb.2022.906312

Djokic L, Stankovic N, Galic I, Moric I, Radakovic N, Šegan S, Pavic A, Senerovic L. Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo. in Frontiers in Microbiology. 2022;13:906312.
doi:10.3389/fmicb.2022.906312 .

Djokic, Lidija, Stankovic, Nada, Galic, Ivana, Moric, Ivana, Radakovic, Natasa, Šegan, Sandra, Pavic, Aleksandar, Senerovic, Lidija, "Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo" in Frontiers in Microbiology, 13 (2022):906312,
https://doi.org/10.3389/fmicb.2022.906312 . .

TY  - CHAP
AU  - Senerovic, Lidija
AU  - Moric, Ivana
AU  - Milivojevic, Dusan
AU  - Opsenica, Dejan
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4459
AB  - The rapid emergence of antibiotic-resistant pathogens presents a global healthcare challenge. Bacteria control their virulence, motility, and biofilm formation, all of them being required for establishing pathogenicity, through a cell density-dependent communication system known as quorum sensing (QS). QS comprises production of extracellular signaling molecules, their detection, and population-wide response involving regulation of the virulence genes expression. Inhibition of QS affects virulence and reduces harmful effects to the host and as such presents a promising strategy to fight antibiotic-resistant infections. Multiresistant Pseudomonas aeruginosa belogns to the group of most critical pathogens for which the introduction of new therapeutics is imperative. In the search for novel therapeutics nature continues to be inexhaustible source of bioactive scaffolds, which provide the bases for structure-based rational drug design enabling further exploitation of diverse natural structures. This review describes bacterial QS systems, highlights strategies for their manipulation, overviews nature-inspired antivirulence molecules primarily against P. aeruginosa, and discusses their perspectives.
PB  - Elsevier
T2  - Biodiversity and Biomedicine
T1  - Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections
SP  - 497
EP  - 523
DO  - 10.1016/B978-0-12-819541-3.00025-6
ER  - 

@inbook{
author = "Senerovic, Lidija and Moric, Ivana and Milivojevic, Dusan and Opsenica, Dejan",
year = "2020",
abstract = "The rapid emergence of antibiotic-resistant pathogens presents a global healthcare challenge. Bacteria control their virulence, motility, and biofilm formation, all of them being required for establishing pathogenicity, through a cell density-dependent communication system known as quorum sensing (QS). QS comprises production of extracellular signaling molecules, their detection, and population-wide response involving regulation of the virulence genes expression. Inhibition of QS affects virulence and reduces harmful effects to the host and as such presents a promising strategy to fight antibiotic-resistant infections. Multiresistant Pseudomonas aeruginosa belogns to the group of most critical pathogens for which the introduction of new therapeutics is imperative. In the search for novel therapeutics nature continues to be inexhaustible source of bioactive scaffolds, which provide the bases for structure-based rational drug design enabling further exploitation of diverse natural structures. This review describes bacterial QS systems, highlights strategies for their manipulation, overviews nature-inspired antivirulence molecules primarily against P. aeruginosa, and discusses their perspectives.",
publisher = "Elsevier",
journal = "Biodiversity and Biomedicine",
booktitle = "Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections",
pages = "497-523",
doi = "10.1016/B978-0-12-819541-3.00025-6"
}

Senerovic, L., Moric, I., Milivojevic, D.,& Opsenica, D.. (2020). Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections. in Biodiversity and Biomedicine
Elsevier., 497-523.
https://doi.org/10.1016/B978-0-12-819541-3.00025-6

Senerovic L, Moric I, Milivojevic D, Opsenica D. Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections. in Biodiversity and Biomedicine. 2020;:497-523.
doi:10.1016/B978-0-12-819541-3.00025-6 .

Senerovic, Lidija, Moric, Ivana, Milivojevic, Dusan, Opsenica, Dejan, "Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections" in Biodiversity and Biomedicine (2020):497-523,
https://doi.org/10.1016/B978-0-12-819541-3.00025-6 . .

TY  - JOUR
AU  - Aleksic, Ivana
AU  - Jeremić, Jelena
AU  - Milivojevic, Dusan
AU  - Ilić-Tomić, Tatjana
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3198
AB  - Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.
PB  - American Chemical Society (ACS)
T2  - ACS Chemical Biology
T1  - N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa
VL  - 14
IS  - 12
SP  - 2800
EP  - 2809
DO  - 10.1021/acschembio.9b00682
ER  - 

@article{
author = "Aleksic, Ivana and Jeremić, Jelena and Milivojevic, Dusan and Ilić-Tomić, Tatjana and Šegan, Sandra and Zlatović, Mario and Opsenica, Dejan and Senerovic, Lidija",
year = "2019",
abstract = "Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.",
publisher = "American Chemical Society (ACS)",
journal = "ACS Chemical Biology",
title = "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa",
volume = "14",
number = "12",
pages = "2800-2809",
doi = "10.1021/acschembio.9b00682"
}

Aleksic, I., Jeremić, J., Milivojevic, D., Ilić-Tomić, T., Šegan, S., Zlatović, M., Opsenica, D.,& Senerovic, L.. (2019). N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology
American Chemical Society (ACS)., 14(12), 2800-2809.
https://doi.org/10.1021/acschembio.9b00682

Aleksic I, Jeremić J, Milivojevic D, Ilić-Tomić T, Šegan S, Zlatović M, Opsenica D, Senerovic L. N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology. 2019;14(12):2800-2809.
doi:10.1021/acschembio.9b00682 .

Aleksic, Ivana, Jeremić, Jelena, Milivojevic, Dusan, Ilić-Tomić, Tatjana, Šegan, Sandra, Zlatović, Mario, Opsenica, Dejan, Senerovic, Lidija, "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa" in ACS Chemical Biology, 14, no. 12 (2019):2800-2809,
https://doi.org/10.1021/acschembio.9b00682 . .

TY  - JOUR
AU  - Aleksic, Ivana
AU  - Jeremić, Jelena
AU  - Milivojevic, Dusan
AU  - Ilić-Tomić, Tatjana
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3198
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3341
AB  - Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.
PB  - American Chemical Society (ACS)
T2  - ACS Chemical Biology
T1  - N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa
VL  - 14
IS  - 12
SP  - 2800
EP  - 2809
DO  - 10.1021/acschembio.9b00682
ER  - 

@article{
author = "Aleksic, Ivana and Jeremić, Jelena and Milivojevic, Dusan and Ilić-Tomić, Tatjana and Šegan, Sandra and Zlatović, Mario and Opsenica, Dejan and Senerovic, Lidija",
year = "2019",
abstract = "Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.",
publisher = "American Chemical Society (ACS)",
journal = "ACS Chemical Biology",
title = "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa",
volume = "14",
number = "12",
pages = "2800-2809",
doi = "10.1021/acschembio.9b00682"
}

Aleksic, I., Jeremić, J., Milivojevic, D., Ilić-Tomić, T., Šegan, S., Zlatović, M., Opsenica, D.,& Senerovic, L.. (2019). N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology
American Chemical Society (ACS)., 14(12), 2800-2809.
https://doi.org/10.1021/acschembio.9b00682

Aleksic I, Jeremić J, Milivojevic D, Ilić-Tomić T, Šegan S, Zlatović M, Opsenica D, Senerovic L. N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology. 2019;14(12):2800-2809.
doi:10.1021/acschembio.9b00682 .

Aleksic, Ivana, Jeremić, Jelena, Milivojevic, Dusan, Ilić-Tomić, Tatjana, Šegan, Sandra, Zlatović, Mario, Opsenica, Dejan, Senerovic, Lidija, "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa" in ACS Chemical Biology, 14, no. 12 (2019):2800-2809,
https://doi.org/10.1021/acschembio.9b00682 . .

TY  - CHAP
AU  - Senerovic, Lidija
AU  - Opsenica, Dejan
AU  - Moric, Ivana
AU  - Aleksic, Ivana
AU  - Spasić, Marta
AU  - Vasiljevic, Branka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3094
AB  - Infective diseases have become health threat of
a global proportion due to appearance and
spread of microorganisms resistant to majority
of therapeutics currently used for their treatment.
Therefore, there is a constant need for
development of new antimicrobial agents, as
well as novel therapeutic strategies.
Quinolines and quinolones, isolated from
plants, animals, and microorganisms, have
demonstrated numerous biological activities
such as antimicrobial, insecticidal, antiinflammatory,
antiplatelet, and antitumor. For
more than two centuries quinoline/quinolone
moiety has been used as a scaffold for drug
development and even today it represents an
inexhaustible inspiration for design and development
of novel semi-synthetic or synthetic
agents exhibiting broad spectrum of
bioactivities. The structural diversity of
synthetized compounds provides high and
selective activity attained through different
mechanisms of action, as well as low toxicity
on human cells. This review describes quinoline
and quinolone derivatives with
antibacterial, antifungal, anti-virulent,
antiviral, and anti-parasitic activities with the
focus on the last 10 years literature.
PB  - Springer Nature
T2  - Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health
T1  - Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents
DO  - 10.1007/5584_2019_428
ER  - 

@inbook{
author = "Senerovic, Lidija and Opsenica, Dejan and Moric, Ivana and Aleksic, Ivana and Spasić, Marta and Vasiljevic, Branka",
year = "2019",
abstract = "Infective diseases have become health threat of
a global proportion due to appearance and
spread of microorganisms resistant to majority
of therapeutics currently used for their treatment.
Therefore, there is a constant need for
development of new antimicrobial agents, as
well as novel therapeutic strategies.
Quinolines and quinolones, isolated from
plants, animals, and microorganisms, have
demonstrated numerous biological activities
such as antimicrobial, insecticidal, antiinflammatory,
antiplatelet, and antitumor. For
more than two centuries quinoline/quinolone
moiety has been used as a scaffold for drug
development and even today it represents an
inexhaustible inspiration for design and development
of novel semi-synthetic or synthetic
agents exhibiting broad spectrum of
bioactivities. The structural diversity of
synthetized compounds provides high and
selective activity attained through different
mechanisms of action, as well as low toxicity
on human cells. This review describes quinoline
and quinolone derivatives with
antibacterial, antifungal, anti-virulent,
antiviral, and anti-parasitic activities with the
focus on the last 10 years literature.",
publisher = "Springer Nature",
journal = "Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health",
booktitle = "Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents",
doi = "10.1007/5584_2019_428"
}

Senerovic, L., Opsenica, D., Moric, I., Aleksic, I., Spasić, M.,& Vasiljevic, B.. (2019). Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents. in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health
Springer Nature..
https://doi.org/10.1007/5584_2019_428

Senerovic L, Opsenica D, Moric I, Aleksic I, Spasić M, Vasiljevic B. Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents. in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health. 2019;.
doi:10.1007/5584_2019_428 .

Senerovic, Lidija, Opsenica, Dejan, Moric, Ivana, Aleksic, Ivana, Spasić, Marta, Vasiljevic, Branka, "Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents" in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health (2019),
https://doi.org/10.1007/5584_2019_428 . .

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Ristivojevic, Petar
AU  - Pavić, Aleksandar
AU  - Radojevic, Ivana
AU  - Čomić, Ljiljana R.
AU  - Vasiljevic, Branka
AU  - Opsenica, Dejan
AU  - Milojković-Opsenica, Dušanka
AU  - Senerovic, Lidija
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2310
AB  - Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.
PB  - Elsevier Ireland Ltd, Clare
T2  - Journal of Ethnopharmacology
T1  - Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts
VL  - 222
SP  - 148
EP  - 158
DO  - 10.1016/j.jep.2018.05.005
ER  - 

@article{
author = "Aleksić, Ivana and Ristivojevic, Petar and Pavić, Aleksandar and Radojevic, Ivana and Čomić, Ljiljana R. and Vasiljevic, Branka and Opsenica, Dejan and Milojković-Opsenica, Dušanka and Senerovic, Lidija",
year = "2018",
abstract = "Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Journal of Ethnopharmacology",
title = "Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts",
volume = "222",
pages = "148-158",
doi = "10.1016/j.jep.2018.05.005"
}

Aleksić, I., Ristivojevic, P., Pavić, A., Radojevic, I., Čomić, L. R., Vasiljevic, B., Opsenica, D., Milojković-Opsenica, D.,& Senerovic, L.. (2018). Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. in Journal of Ethnopharmacology
Elsevier Ireland Ltd, Clare., 222, 148-158.
https://doi.org/10.1016/j.jep.2018.05.005

Aleksić I, Ristivojevic P, Pavić A, Radojevic I, Čomić LR, Vasiljevic B, Opsenica D, Milojković-Opsenica D, Senerovic L. Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. in Journal of Ethnopharmacology. 2018;222:148-158.
doi:10.1016/j.jep.2018.05.005 .

Aleksić, Ivana, Ristivojevic, Petar, Pavić, Aleksandar, Radojevic, Ivana, Čomić, Ljiljana R., Vasiljevic, Branka, Opsenica, Dejan, Milojković-Opsenica, Dušanka, Senerovic, Lidija, "Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts" in Journal of Ethnopharmacology, 222 (2018):148-158,
https://doi.org/10.1016/j.jep.2018.05.005 . .

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Šegan, Sandra
AU  - Andrić, Filip
AU  - Zlatović, Mario
AU  - Moric, Ivana
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2270
AB  - Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.
PB  - American Chemical Society (ACS)
T2  - Acs Chemical Biology
T1  - Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa
VL  - 12
IS  - 5
SP  - 1425
EP  - 1434
DO  - 10.1021/acschembio.6b01149
ER  - 

@article{
author = "Aleksić, Ivana and Šegan, Sandra and Andrić, Filip and Zlatović, Mario and Moric, Ivana and Opsenica, Dejan and Senerovic, Lidija",
year = "2017",
abstract = "Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.",
publisher = "American Chemical Society (ACS)",
journal = "Acs Chemical Biology",
title = "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa",
volume = "12",
number = "5",
pages = "1425-1434",
doi = "10.1021/acschembio.6b01149"
}

Aleksić, I., Šegan, S., Andrić, F., Zlatović, M., Moric, I., Opsenica, D.,& Senerovic, L.. (2017). Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology
American Chemical Society (ACS)., 12(5), 1425-1434.
https://doi.org/10.1021/acschembio.6b01149

Aleksić I, Šegan S, Andrić F, Zlatović M, Moric I, Opsenica D, Senerovic L. Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology. 2017;12(5):1425-1434.
doi:10.1021/acschembio.6b01149 .

Aleksić, Ivana, Šegan, Sandra, Andrić, Filip, Zlatović, Mario, Moric, Ivana, Opsenica, Dejan, Senerovic, Lidija, "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa" in Acs Chemical Biology, 12, no. 5 (2017):1425-1434,
https://doi.org/10.1021/acschembio.6b01149 . .

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Šegan, Sandra
AU  - Andrić, Filip
AU  - Zlatović, Mario
AU  - Moric, Ivana
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2983
AB  - Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.
PB  - American Chemical Society (ACS)
T2  - Acs Chemical Biology
T1  - Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa
VL  - 12
IS  - 5
SP  - 1425
EP  - 1434
DO  - 10.1021/acschembio.6b01149
ER  - 

@article{
author = "Aleksić, Ivana and Šegan, Sandra and Andrić, Filip and Zlatović, Mario and Moric, Ivana and Opsenica, Dejan and Senerovic, Lidija",
year = "2017",
abstract = "Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.",
publisher = "American Chemical Society (ACS)",
journal = "Acs Chemical Biology",
title = "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa",
volume = "12",
number = "5",
pages = "1425-1434",
doi = "10.1021/acschembio.6b01149"
}

Aleksić, I., Šegan, S., Andrić, F., Zlatović, M., Moric, I., Opsenica, D.,& Senerovic, L.. (2017). Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology
American Chemical Society (ACS)., 12(5), 1425-1434.
https://doi.org/10.1021/acschembio.6b01149

Aleksić I, Šegan S, Andrić F, Zlatović M, Moric I, Opsenica D, Senerovic L. Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology. 2017;12(5):1425-1434.
doi:10.1021/acschembio.6b01149 .

Aleksić, Ivana, Šegan, Sandra, Andrić, Filip, Zlatović, Mario, Moric, Ivana, Opsenica, Dejan, Senerovic, Lidija, "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa" in Acs Chemical Biology, 12, no. 5 (2017):1425-1434,
https://doi.org/10.1021/acschembio.6b01149 . .