TY  - JOUR
AU  - Ćurčić, Jovana
AU  - Dinić, Miroslav
AU  - Novović, Katarina
AU  - Vasiljević, Zorica
AU  - Kojić, Milan
AU  - Jovčić, Branko
AU  - Malešević, Milka
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/864
AB  - Infections caused by multidrug-resistant pathogens are one of the biggest challenges facing the healthcare system today. Quorum quenching (QQ) enzymes have the potential to be used as innovative enzyme-based antivirulence therapeutics to combat infections caused by multidrug-resistant pathogens. The main objective of this research was to describe the novel YtnP lactonase derived from the clinical isolate Stenotrophomonas maltophilia and to investigate its antivirulence potential against multidrug-resistant Pseudomonas aeruginosa MMA83. YtnP lactonase, the QQ enzyme, belongs to the family of metallo-β-lactamases. The recombinant enzyme has several advantageous biotechnological properties, such as high thermostability, activity in a wide pH range, and no cytotoxic effect. High-performance liquid chromatography analysis revealed the activity of recombinant YtnP lactonase toward a wide range of N-acyl-homoserine lactones (AHLs), quorum sensing signaling molecules, with a higher preference for long-chain AHLs. Recombinant YtnP lactonase was shown to inhibit P. aeruginosa MMA83 biofilm formation, induce biofilm decomposition, and reduce extracellular virulence factors production. Moreover, the lifespan of MMA83-infected Caenorhabditis elegans was prolonged with YtnP lactonase treatment. YtnP lactonase showed synergistic inhibitory activity in combination with gentamicin and acted additively with meropenem against MMA83. The described properties make YtnP lactonase a promising therapeutic candidate for the development of next-generation antivirulence agents.
T2  - International Journal of Biological Macromolecules
T1  - A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo
SP  - 130421
DO  - 10.1016/j.ijbiomac.2024.130421
ER  - 

@article{
author = "Ćurčić, Jovana and Dinić, Miroslav and Novović, Katarina and Vasiljević, Zorica and Kojić, Milan and Jovčić, Branko and Malešević, Milka",
year = "2024",
abstract = "Infections caused by multidrug-resistant pathogens are one of the biggest challenges facing the healthcare system today. Quorum quenching (QQ) enzymes have the potential to be used as innovative enzyme-based antivirulence therapeutics to combat infections caused by multidrug-resistant pathogens. The main objective of this research was to describe the novel YtnP lactonase derived from the clinical isolate Stenotrophomonas maltophilia and to investigate its antivirulence potential against multidrug-resistant Pseudomonas aeruginosa MMA83. YtnP lactonase, the QQ enzyme, belongs to the family of metallo-β-lactamases. The recombinant enzyme has several advantageous biotechnological properties, such as high thermostability, activity in a wide pH range, and no cytotoxic effect. High-performance liquid chromatography analysis revealed the activity of recombinant YtnP lactonase toward a wide range of N-acyl-homoserine lactones (AHLs), quorum sensing signaling molecules, with a higher preference for long-chain AHLs. Recombinant YtnP lactonase was shown to inhibit P. aeruginosa MMA83 biofilm formation, induce biofilm decomposition, and reduce extracellular virulence factors production. Moreover, the lifespan of MMA83-infected Caenorhabditis elegans was prolonged with YtnP lactonase treatment. YtnP lactonase showed synergistic inhibitory activity in combination with gentamicin and acted additively with meropenem against MMA83. The described properties make YtnP lactonase a promising therapeutic candidate for the development of next-generation antivirulence agents.",
journal = "International Journal of Biological Macromolecules",
title = "A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo",
pages = "130421",
doi = "10.1016/j.ijbiomac.2024.130421"
}

Ćurčić, J., Dinić, M., Novović, K., Vasiljević, Z., Kojić, M., Jovčić, B.,& Malešević, M.. (2024). A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo. in International Journal of Biological Macromolecules, 130421.
https://doi.org/10.1016/j.ijbiomac.2024.130421

Ćurčić J, Dinić M, Novović K, Vasiljević Z, Kojić M, Jovčić B, Malešević M. A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo. in International Journal of Biological Macromolecules. 2024;:130421.
doi:10.1016/j.ijbiomac.2024.130421 .

Ćurčić, Jovana, Dinić, Miroslav, Novović, Katarina, Vasiljević, Zorica, Kojić, Milan, Jovčić, Branko, Malešević, Milka, "A novel thermostable YtnP lactonase from Stenotrophomonas maltophilia inhibits Pseudomonas aeruginosa virulence in vitro and in vivo" in International Journal of Biological Macromolecules (2024):130421,
https://doi.org/10.1016/j.ijbiomac.2024.130421 . .

TY  - CONF
AU  - Ćurčić, Jovana
AU  - Jakovljević, Stefan
AU  - Novović, Katarina
AU  - Vasiljević, Zorica
AU  - Kojić, Milan
AU  - Jovčić, Branko
AU  - Malešević, Milka
PY  - 2023
UR  - http://intor.torlakinstitut.com/handle/123456789/803
AB  - Introduction: Quorum quenching (QQ) isthe enzymatic degradation of cell-to-cellsignaling molecules.
In this study, the potential of the novel YtnP lactonase, the quorum quenching enzyme derived from S.
maltophilia, to reduce P. aeruginosa quorum sensing and virulence factor gene expression was investigated.
Methods: MMA83 culture (adjusted to 1.5x105 CFU/ml) was treated with recombinant YtnP lactonase
(final concentration 50 μg/ml) at 37°C for 12 hours under aeration. RNA isolation of the treated and untreated MMA83 culture was performed using the RNeasy Mini Kit (Qiagen, Germany) according to the
protocol. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR), was used to analyze
the effect ofYtnP lactonase on the relative mRNA levels of the LasI/LasR, RhiI/RhiR, and PQS signaling network genes of P. aeruginosa MMA83 and virulence factor genes. The rpsL was used as an endogenous
control to normalize obtained data following the 2-ΔΔCt method.
Results: The QS genes belonging to three QS networks – LasI/LasR, RhiI/RhiR, and PQS of P. aeruginosa
MMA83 treated with YtnP lactonase were significantly downregulated. The RT -qPCR results show that
treatment with YtnP-lactonase decreased the relative mRNA levels of genes involved in the production
of elastase (lasB approximately 2-fold), alginate (algK approximately 2.2-fold), pyocyanin (phzM approximately 3.5-fold), pyoverdin (pvdS approximately 2-fold), and rhamnolipid (rhlC approximately 4-fold).
These results suggest that YtnP lactonase exerts an antivirulence effect at the transcription level.
Conclusion: YtnP lactonase, a quorum quenching (QQ) enzyme, has the potential to be used as an innovative enzyme-based antivirulence therapeutic to combat infections caused by P. aeruginosa.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - A novel YtnP lactonase reduces the expression of p. aeruginosa MMA83 quorum sensing andvirulence factors gene expression
EP  - 121
SP  - 121
UR  - https://hdl.handle.net/21.15107/rcub_intor_803
ER  - 

@conference{
author = "Ćurčić, Jovana and Jakovljević, Stefan and Novović, Katarina and Vasiljević, Zorica and Kojić, Milan and Jovčić, Branko and Malešević, Milka",
year = "2023",
abstract = "Introduction: Quorum quenching (QQ) isthe enzymatic degradation of cell-to-cellsignaling molecules.
In this study, the potential of the novel YtnP lactonase, the quorum quenching enzyme derived from S.
maltophilia, to reduce P. aeruginosa quorum sensing and virulence factor gene expression was investigated.
Methods: MMA83 culture (adjusted to 1.5x105 CFU/ml) was treated with recombinant YtnP lactonase
(final concentration 50 μg/ml) at 37°C for 12 hours under aeration. RNA isolation of the treated and untreated MMA83 culture was performed using the RNeasy Mini Kit (Qiagen, Germany) according to the
protocol. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR), was used to analyze
the effect ofYtnP lactonase on the relative mRNA levels of the LasI/LasR, RhiI/RhiR, and PQS signaling network genes of P. aeruginosa MMA83 and virulence factor genes. The rpsL was used as an endogenous
control to normalize obtained data following the 2-ΔΔCt method.
Results: The QS genes belonging to three QS networks – LasI/LasR, RhiI/RhiR, and PQS of P. aeruginosa
MMA83 treated with YtnP lactonase were significantly downregulated. The RT -qPCR results show that
treatment with YtnP-lactonase decreased the relative mRNA levels of genes involved in the production
of elastase (lasB approximately 2-fold), alginate (algK approximately 2.2-fold), pyocyanin (phzM approximately 3.5-fold), pyoverdin (pvdS approximately 2-fold), and rhamnolipid (rhlC approximately 4-fold).
These results suggest that YtnP lactonase exerts an antivirulence effect at the transcription level.
Conclusion: YtnP lactonase, a quorum quenching (QQ) enzyme, has the potential to be used as an innovative enzyme-based antivirulence therapeutic to combat infections caused by P. aeruginosa.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "A novel YtnP lactonase reduces the expression of p. aeruginosa MMA83 quorum sensing andvirulence factors gene expression",
pages = "121-121",
url = "https://hdl.handle.net/21.15107/rcub_intor_803"
}

Ćurčić, J., Jakovljević, S., Novović, K., Vasiljević, Z., Kojić, M., Jovčić, B.,& Malešević, M.. (2023). A novel YtnP lactonase reduces the expression of p. aeruginosa MMA83 quorum sensing andvirulence factors gene expression. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 121-121.
https://hdl.handle.net/21.15107/rcub_intor_803

Ćurčić J, Jakovljević S, Novović K, Vasiljević Z, Kojić M, Jovčić B, Malešević M. A novel YtnP lactonase reduces the expression of p. aeruginosa MMA83 quorum sensing andvirulence factors gene expression. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:121-121.
https://hdl.handle.net/21.15107/rcub_intor_803 .

Ćurčić, Jovana, Jakovljević, Stefan, Novović, Katarina, Vasiljević, Zorica, Kojić, Milan, Jovčić, Branko, Malešević, Milka, "A novel YtnP lactonase reduces the expression of p. aeruginosa MMA83 quorum sensing andvirulence factors gene expression" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):121-121,
https://hdl.handle.net/21.15107/rcub_intor_803 .

TY  - JOUR
AU  - Filipić, Brankica
AU  - Malešević, Milka
AU  - Vasiljević, Zorica
AU  - Novović, Katarina
AU  - Kojić, Milan
AU  - Jovčić, Branko
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/724
AB  - Trimethoprim-sulfamethoxazole (SXT) is the preferable treatment option of the infections caused by Achromobacter spp. Our study aimed to analyze the SXT resistance of 98 Achromobacter spp. isolates from pediatric patients, among which 33 isolates were SXT-resistant. The presence of intI1 was screened by PCR and genome sequence analyses. The intI1 gene was detected in 10 of SXT-resistant isolates that had shorter intI1 PCR fragments named intI1S. Structural changes in intI1S were confirmed by genome sequencing and analyses which revealed 86 amino acids deletion in IntI1S protein compared to canonical IntI1 protein. All IntI1S isolates were of non-CF origin. Pan-genome analysis of intI1S bearing A. xylosoxidans isolates comprised 9052 genes, with the core genome consisting of 5455 protein-coding genes. Results in this study indicate that IntI1S isolates were derived from clinical settings and that cystic fibrosis (CF) patients were potential reservoirs for healthcare-associated infections that occurred in non-CF patients.
PB  - Springer Science and Business Media B.V.
T2  - Folia Microbiologica
T1  - Comparative genomics of trimethoprim-sulfamethoxazole-resistant Achromobacter xylosoxidans clinical isolates from Serbia reveals shortened variant of class 1 integron integrase gene
DO  - 10.1007/s12223-022-01026-8
ER  - 

@article{
author = "Filipić, Brankica and Malešević, Milka and Vasiljević, Zorica and Novović, Katarina and Kojić, Milan and Jovčić, Branko",
year = "2022",
abstract = "Trimethoprim-sulfamethoxazole (SXT) is the preferable treatment option of the infections caused by Achromobacter spp. Our study aimed to analyze the SXT resistance of 98 Achromobacter spp. isolates from pediatric patients, among which 33 isolates were SXT-resistant. The presence of intI1 was screened by PCR and genome sequence analyses. The intI1 gene was detected in 10 of SXT-resistant isolates that had shorter intI1 PCR fragments named intI1S. Structural changes in intI1S were confirmed by genome sequencing and analyses which revealed 86 amino acids deletion in IntI1S protein compared to canonical IntI1 protein. All IntI1S isolates were of non-CF origin. Pan-genome analysis of intI1S bearing A. xylosoxidans isolates comprised 9052 genes, with the core genome consisting of 5455 protein-coding genes. Results in this study indicate that IntI1S isolates were derived from clinical settings and that cystic fibrosis (CF) patients were potential reservoirs for healthcare-associated infections that occurred in non-CF patients.",
publisher = "Springer Science and Business Media B.V.",
journal = "Folia Microbiologica",
title = "Comparative genomics of trimethoprim-sulfamethoxazole-resistant Achromobacter xylosoxidans clinical isolates from Serbia reveals shortened variant of class 1 integron integrase gene",
doi = "10.1007/s12223-022-01026-8"
}

Filipić, B., Malešević, M., Vasiljević, Z., Novović, K., Kojić, M.,& Jovčić, B.. (2022). Comparative genomics of trimethoprim-sulfamethoxazole-resistant Achromobacter xylosoxidans clinical isolates from Serbia reveals shortened variant of class 1 integron integrase gene. in Folia Microbiologica
Springer Science and Business Media B.V...
https://doi.org/10.1007/s12223-022-01026-8

Filipić B, Malešević M, Vasiljević Z, Novović K, Kojić M, Jovčić B. Comparative genomics of trimethoprim-sulfamethoxazole-resistant Achromobacter xylosoxidans clinical isolates from Serbia reveals shortened variant of class 1 integron integrase gene. in Folia Microbiologica. 2022;.
doi:10.1007/s12223-022-01026-8 .

Filipić, Brankica, Malešević, Milka, Vasiljević, Zorica, Novović, Katarina, Kojić, Milan, Jovčić, Branko, "Comparative genomics of trimethoprim-sulfamethoxazole-resistant Achromobacter xylosoxidans clinical isolates from Serbia reveals shortened variant of class 1 integron integrase gene" in Folia Microbiologica (2022),
https://doi.org/10.1007/s12223-022-01026-8 . .

TY  - JOUR
AU  - Malešević, Milka
AU  - Stanisavljević, Nemanja
AU  - Novović, Katarina
AU  - Polović, Natalija
AU  - Vasiljević, Zorica
AU  - Kojić, Milan
AU  - Jovčić, Branko
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1338
UR  - http://intor.torlakinstitut.com/handle/123456789/705
AB  - Burkholderia cepacia is well known as the causative agent of infections in humans where often shares niche with other pathogens, like Pseudomonas aeruginosa. Clinical isolate Burkholderia sp. BCC4135 was selected due to its strong quorum quenching (QQ) activity. Whole genome sequencing unveiled this isolate as B. cepacia with unique sequence type ST1485 and a myriad of genes belonging to resistome and virulome. Two QQ lactonases YtnP and Y2-aiiA originated from B. cepacia BCC4135 were cloned, expressed, and functionally characterized. They were active against a broad substrate spectrum of the N-acyl-homoserine lactones (AHLs). The YtnP lactonase was inactive, while Y2-aiiA was active against N-tetradecanoyl-DL-homoserine lactone (C14-HSL) which could imply the difference in their biological roles from the aspect of its quorum sensing (QS) autoregulation and interference with the QS systems of bacteria residing within the same niche. Both YtnP and Y2-aiiA were able to attenuate virulence potential of P. aeruginosa MMA83 clinical isolate declining its biofilm formation and virulence factors production. B. cepacia BCC4135 lactonases interfered with the las, rhl, and even pqs QS circuit of P. aeruginosa MMA83 transcription and the effect of combined enzymes was even more prominent. B. cepacia BCC4135 also employs the CepI/R QS system for governing its own virulence traits and possibly self-regulates the QQ/QS network through the different expression and activity of YtnP and/or Y2-aiiA. Our findings pointed out that BCC4135 lactonases could be exploited as an effective antivirulence drugs against P. aeruginosa and gave us a new insight into B. cepacia QQ/QS machinery.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
T2  - Microbial Pathogenesis
T1  - Burkholderia cepacia YtnP and Y2-aiiA lactonases inhibit virulence of Pseudomonas aeruginosa via quorum quenching activity
VL  - 149
DO  - 10.1016/j.micpath.2020.104561
ER  - 

@article{
author = "Malešević, Milka and Stanisavljević, Nemanja and Novović, Katarina and Polović, Natalija and Vasiljević, Zorica and Kojić, Milan and Jovčić, Branko",
year = "2020",
abstract = "Burkholderia cepacia is well known as the causative agent of infections in humans where often shares niche with other pathogens, like Pseudomonas aeruginosa. Clinical isolate Burkholderia sp. BCC4135 was selected due to its strong quorum quenching (QQ) activity. Whole genome sequencing unveiled this isolate as B. cepacia with unique sequence type ST1485 and a myriad of genes belonging to resistome and virulome. Two QQ lactonases YtnP and Y2-aiiA originated from B. cepacia BCC4135 were cloned, expressed, and functionally characterized. They were active against a broad substrate spectrum of the N-acyl-homoserine lactones (AHLs). The YtnP lactonase was inactive, while Y2-aiiA was active against N-tetradecanoyl-DL-homoserine lactone (C14-HSL) which could imply the difference in their biological roles from the aspect of its quorum sensing (QS) autoregulation and interference with the QS systems of bacteria residing within the same niche. Both YtnP and Y2-aiiA were able to attenuate virulence potential of P. aeruginosa MMA83 clinical isolate declining its biofilm formation and virulence factors production. B. cepacia BCC4135 lactonases interfered with the las, rhl, and even pqs QS circuit of P. aeruginosa MMA83 transcription and the effect of combined enzymes was even more prominent. B. cepacia BCC4135 also employs the CepI/R QS system for governing its own virulence traits and possibly self-regulates the QQ/QS network through the different expression and activity of YtnP and/or Y2-aiiA. Our findings pointed out that BCC4135 lactonases could be exploited as an effective antivirulence drugs against P. aeruginosa and gave us a new insight into B. cepacia QQ/QS machinery.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
journal = "Microbial Pathogenesis",
title = "Burkholderia cepacia YtnP and Y2-aiiA lactonases inhibit virulence of Pseudomonas aeruginosa via quorum quenching activity",
volume = "149",
doi = "10.1016/j.micpath.2020.104561"
}

Malešević, M., Stanisavljević, N., Novović, K., Polović, N., Vasiljević, Z., Kojić, M.,& Jovčić, B.. (2020). Burkholderia cepacia YtnP and Y2-aiiA lactonases inhibit virulence of Pseudomonas aeruginosa via quorum quenching activity. in Microbial Pathogenesis
Academic Press Ltd- Elsevier Science Ltd, London., 149.
https://doi.org/10.1016/j.micpath.2020.104561

Malešević M, Stanisavljević N, Novović K, Polović N, Vasiljević Z, Kojić M, Jovčić B. Burkholderia cepacia YtnP and Y2-aiiA lactonases inhibit virulence of Pseudomonas aeruginosa via quorum quenching activity. in Microbial Pathogenesis. 2020;149.
doi:10.1016/j.micpath.2020.104561 .

Malešević, Milka, Stanisavljević, Nemanja, Novović, Katarina, Polović, Natalija, Vasiljević, Zorica, Kojić, Milan, Jovčić, Branko, "Burkholderia cepacia YtnP and Y2-aiiA lactonases inhibit virulence of Pseudomonas aeruginosa via quorum quenching activity" in Microbial Pathogenesis, 149 (2020),
https://doi.org/10.1016/j.micpath.2020.104561 . .

TY  - JOUR
AU  - Lilić, Branislav
AU  - Filipić, Brankica
AU  - Malešević, Milka
AU  - Novović, Katarina
AU  - Vasiljević, Zorica
AU  - Kojić, Milan
AU  - Jovčić, Branko
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1278
UR  - http://intor.torlakinstitut.com/handle/123456789/742
AB  - The aim of this study was to evaluate the contribution of plasmid-mediated genes and efflux to fluoroquinolone resistance in collection of Achromobacter spp. gathered during a 3-year period. Susceptibility to ciprofloxacin and levofloxacin was tested by disk diffusion and microdilution tests for a collection of 98 Achromobacter spp. clinical isolates. Identification of fluoroquinolone-resistant isolates was performed by sequencing and phylogenetic analyses of the nrdA gene. Genetic relatedness among resistant isolates was determined by pulsed-field gel electrophoresis (PFGE) analysis. The influence of an H+ conductor cyanide m-chlorophenyl hydrazone (CCCP) and a resistance-nodulation-division-type efflux pump inhibitor phenylalanine-arginine beta-naphthylamide (PAN) on minimal inhibitory concentration (MIC) value was evaluated by broth microdilution. The presence of the plasmid-mediated qnrA, qnrB, qnrC, qnrS, and aac-(6)-Ib-cr genes was investigated by PCR and sequencing. Achromobacter spp. isolates that were resistant or intermediately resistant to fluoroquinolones in disk diffusion tests (44/98) were subjected to microdilution. As a result, 20/98 isolates were confirmed to be resistant to ciprofloxacin while 10/98 was resistant to levofloxacin. CCCP decreased twofold MIC value for ciprofloxacin in six isolates and more than 16 times in one isolate, while MIC value for levofloxacin was decreased in all isolates (twofold to more than eightfold). Fluoroquinolone-resistant isolates were identified as A. xylosoxidans with the nrdA gene sequencing. PFGE revealed that resistant isolates belonged to seven different genotypes. Ten isolates belonging to four genotypes were positive for the aac-(6)-Ib-cr gene. Although resistance to fluoroquinolones was not widespread among analyzed isolates, detected contribution of efflux pumps and the presence of the aac-(6)-Ib-cr gene present a platform for emergence of more resistant strains.
PB  - Springer, Dordrecht
T2  - Folia Microbiologica
T1  - Fluoroquinolone-resistant Achromobacter xylosoxidans clinical isolates from Serbia: high prevalence of the aac-(6)-Ib-cr gene among resistant isolates
EP  - 159
IS  - 2
SP  - 153
VL  - 64
DO  - 10.1007/s12223-018-0639-7
ER  - 

@article{
author = "Lilić, Branislav and Filipić, Brankica and Malešević, Milka and Novović, Katarina and Vasiljević, Zorica and Kojić, Milan and Jovčić, Branko",
year = "2019",
abstract = "The aim of this study was to evaluate the contribution of plasmid-mediated genes and efflux to fluoroquinolone resistance in collection of Achromobacter spp. gathered during a 3-year period. Susceptibility to ciprofloxacin and levofloxacin was tested by disk diffusion and microdilution tests for a collection of 98 Achromobacter spp. clinical isolates. Identification of fluoroquinolone-resistant isolates was performed by sequencing and phylogenetic analyses of the nrdA gene. Genetic relatedness among resistant isolates was determined by pulsed-field gel electrophoresis (PFGE) analysis. The influence of an H+ conductor cyanide m-chlorophenyl hydrazone (CCCP) and a resistance-nodulation-division-type efflux pump inhibitor phenylalanine-arginine beta-naphthylamide (PAN) on minimal inhibitory concentration (MIC) value was evaluated by broth microdilution. The presence of the plasmid-mediated qnrA, qnrB, qnrC, qnrS, and aac-(6)-Ib-cr genes was investigated by PCR and sequencing. Achromobacter spp. isolates that were resistant or intermediately resistant to fluoroquinolones in disk diffusion tests (44/98) were subjected to microdilution. As a result, 20/98 isolates were confirmed to be resistant to ciprofloxacin while 10/98 was resistant to levofloxacin. CCCP decreased twofold MIC value for ciprofloxacin in six isolates and more than 16 times in one isolate, while MIC value for levofloxacin was decreased in all isolates (twofold to more than eightfold). Fluoroquinolone-resistant isolates were identified as A. xylosoxidans with the nrdA gene sequencing. PFGE revealed that resistant isolates belonged to seven different genotypes. Ten isolates belonging to four genotypes were positive for the aac-(6)-Ib-cr gene. Although resistance to fluoroquinolones was not widespread among analyzed isolates, detected contribution of efflux pumps and the presence of the aac-(6)-Ib-cr gene present a platform for emergence of more resistant strains.",
publisher = "Springer, Dordrecht",
journal = "Folia Microbiologica",
title = "Fluoroquinolone-resistant Achromobacter xylosoxidans clinical isolates from Serbia: high prevalence of the aac-(6)-Ib-cr gene among resistant isolates",
pages = "159-153",
number = "2",
volume = "64",
doi = "10.1007/s12223-018-0639-7"
}

Lilić, B., Filipić, B., Malešević, M., Novović, K., Vasiljević, Z., Kojić, M.,& Jovčić, B.. (2019). Fluoroquinolone-resistant Achromobacter xylosoxidans clinical isolates from Serbia: high prevalence of the aac-(6)-Ib-cr gene among resistant isolates. in Folia Microbiologica
Springer, Dordrecht., 64(2), 153-159.
https://doi.org/10.1007/s12223-018-0639-7

Lilić B, Filipić B, Malešević M, Novović K, Vasiljević Z, Kojić M, Jovčić B. Fluoroquinolone-resistant Achromobacter xylosoxidans clinical isolates from Serbia: high prevalence of the aac-(6)-Ib-cr gene among resistant isolates. in Folia Microbiologica. 2019;64(2):153-159.
doi:10.1007/s12223-018-0639-7 .

Lilić, Branislav, Filipić, Brankica, Malešević, Milka, Novović, Katarina, Vasiljević, Zorica, Kojić, Milan, Jovčić, Branko, "Fluoroquinolone-resistant Achromobacter xylosoxidans clinical isolates from Serbia: high prevalence of the aac-(6)-Ib-cr gene among resistant isolates" in Folia Microbiologica, 64, no. 2 (2019):153-159,
https://doi.org/10.1007/s12223-018-0639-7 . .

TY  - JOUR
AU  - Madi, Haowa
AU  - Lukić, Jovanka
AU  - Vasiljević, Zorica
AU  - Biocanin, Marjan
AU  - Kojić, Milan
AU  - Jovčić, Branko
AU  - Lozo, Jelena
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/923
UR  - http://intor.torlakinstitut.com/handle/123456789/745
AB  - Background Stenotrophomonas maltophilia is an environmental bacterium and an opportunistic pathogen usually associated with healthcare-associated infections, which has recently been recognized as a globally multi-drug resistant organism. The aim of this study was genotyping and physiological characterization of Stenotrophomonas maltophilia isolated in a large, tertiary care pediatric hospital in Belgrade, Serbia, hosting the national reference cystic fibrosis (CF) center for pediatric and adult patients. Methods We characterized 42 strains of cystic fibrosis (CF) and 46 strains of non-cystic fibrosis (non-CF) origin isolated from 2013 to 2015 in order to investigate their genetic relatedness and phenotypic traits. Genotyping was performed using sequencing of 16S rRNA gene, Pulse Field Gel Electrophoresis (PFGE) and Multi locus sequencing typing (MLST) analysis. Sensitivity to five relevant antimicrobial agents was determined, namely trimethoprim/sulfamethoxazole (TMP/SMX), chloramphenicol, ciprofloxacin, levofloxacin and tetracycline. Surface characteristics, motility, biofilm formation and adhesion to mucin were tested in all strains. Statistical approach was used to determine correlations between obtained results. Results Most of the isolates were not genetically related. Six new sequence types were determined. Strains were uniformly sensitive to all tested antimicrobial agents. The majority of isolates (89.8%) were able to form biofilm with almost equal representation in both CF and non-CF strains. Swimming motility was observed in all strains, while none of them exhibited swarming motility. Among strains able to adhere to mucin, no differences between CF and non-CF isolates were observed. Conclusions High genetic diversity among isolates implies the absence of clonal spread within the hospital. Positive correlation between motility, biofilm formation and adhesion to mucin was demonstrated. Biofilm formation and motility were more pronounced among non-CF than CF isolates.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Genotypic and Phenotypic Characterization of Stenotrophomonas maltophilia Strains from a Pediatric Tertiary Care Hospital in Serbia
IS  - 10
VL  - 11
DO  - 10.1371/journal.pone.0165660
ER  - 

@article{
author = "Madi, Haowa and Lukić, Jovanka and Vasiljević, Zorica and Biocanin, Marjan and Kojić, Milan and Jovčić, Branko and Lozo, Jelena",
year = "2016",
abstract = "Background Stenotrophomonas maltophilia is an environmental bacterium and an opportunistic pathogen usually associated with healthcare-associated infections, which has recently been recognized as a globally multi-drug resistant organism. The aim of this study was genotyping and physiological characterization of Stenotrophomonas maltophilia isolated in a large, tertiary care pediatric hospital in Belgrade, Serbia, hosting the national reference cystic fibrosis (CF) center for pediatric and adult patients. Methods We characterized 42 strains of cystic fibrosis (CF) and 46 strains of non-cystic fibrosis (non-CF) origin isolated from 2013 to 2015 in order to investigate their genetic relatedness and phenotypic traits. Genotyping was performed using sequencing of 16S rRNA gene, Pulse Field Gel Electrophoresis (PFGE) and Multi locus sequencing typing (MLST) analysis. Sensitivity to five relevant antimicrobial agents was determined, namely trimethoprim/sulfamethoxazole (TMP/SMX), chloramphenicol, ciprofloxacin, levofloxacin and tetracycline. Surface characteristics, motility, biofilm formation and adhesion to mucin were tested in all strains. Statistical approach was used to determine correlations between obtained results. Results Most of the isolates were not genetically related. Six new sequence types were determined. Strains were uniformly sensitive to all tested antimicrobial agents. The majority of isolates (89.8%) were able to form biofilm with almost equal representation in both CF and non-CF strains. Swimming motility was observed in all strains, while none of them exhibited swarming motility. Among strains able to adhere to mucin, no differences between CF and non-CF isolates were observed. Conclusions High genetic diversity among isolates implies the absence of clonal spread within the hospital. Positive correlation between motility, biofilm formation and adhesion to mucin was demonstrated. Biofilm formation and motility were more pronounced among non-CF than CF isolates.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Genotypic and Phenotypic Characterization of Stenotrophomonas maltophilia Strains from a Pediatric Tertiary Care Hospital in Serbia",
number = "10",
volume = "11",
doi = "10.1371/journal.pone.0165660"
}

Madi, H., Lukić, J., Vasiljević, Z., Biocanin, M., Kojić, M., Jovčić, B.,& Lozo, J.. (2016). Genotypic and Phenotypic Characterization of Stenotrophomonas maltophilia Strains from a Pediatric Tertiary Care Hospital in Serbia. in PLoS One
Public Library Science, San Francisco., 11(10).
https://doi.org/10.1371/journal.pone.0165660

Madi H, Lukić J, Vasiljević Z, Biocanin M, Kojić M, Jovčić B, Lozo J. Genotypic and Phenotypic Characterization of Stenotrophomonas maltophilia Strains from a Pediatric Tertiary Care Hospital in Serbia. in PLoS One. 2016;11(10).
doi:10.1371/journal.pone.0165660 .

Madi, Haowa, Lukić, Jovanka, Vasiljević, Zorica, Biocanin, Marjan, Kojić, Milan, Jovčić, Branko, Lozo, Jelena, "Genotypic and Phenotypic Characterization of Stenotrophomonas maltophilia Strains from a Pediatric Tertiary Care Hospital in Serbia" in PLoS One, 11, no. 10 (2016),
https://doi.org/10.1371/journal.pone.0165660 . .

TY  - JOUR
AU  - Jovčić, Branko
AU  - Vasiljević, Zorica
AU  - Đukić, Slobodanka
AU  - Topisirović, Ljubiša
AU  - Kojić, Milan
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/541
UR  - http://intor.torlakinstitut.com/handle/123456789/735
AB  - Molecular detection and surveillance of theresistance genes harboured byPseudomonas aeruginosa are becomingincreasingly important in assessing andcontrolling spread and colonization inhospitals, and in guiding the antibiotictreatment of infections. Metallo-blactamase (MBL)-producing P. aeruginosastrains are slowly but steadily increasingwithin hospitals, causing outbreaks and/orhyperendemic situations in some centres,mostly in the Far East and the south ofEurope (Queenan & Bush, 2007). Theglobal dissemination of MBL-producingP. aeruginosa strains has also reached theBalkan region (Lepsanovic et al., 2008;Sardelic et al., 2003). The objective of ourstudy was to detect and characterize P.aeruginosa isolates producing MBLs fromthe 400-bed paediatric tertiary carehospital Mother and Child Health Instituteof Serbia ‘Dr Vukan Cupic’
PB  - Soc General Microbiology, Reading
T2  - Journal of Medical Microbiology
T1  - Emergence of VIM-2 metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates in a paediatric hospital in Serbia
EP  - 869
IS  - 6
SP  - 868
VL  - 60
DO  - 10.1099/jmm.0.029173-0
ER  - 

@article{
author = "Jovčić, Branko and Vasiljević, Zorica and Đukić, Slobodanka and Topisirović, Ljubiša and Kojić, Milan",
year = "2011",
abstract = "Molecular detection and surveillance of theresistance genes harboured byPseudomonas aeruginosa are becomingincreasingly important in assessing andcontrolling spread and colonization inhospitals, and in guiding the antibiotictreatment of infections. Metallo-blactamase (MBL)-producing P. aeruginosastrains are slowly but steadily increasingwithin hospitals, causing outbreaks and/orhyperendemic situations in some centres,mostly in the Far East and the south ofEurope (Queenan & Bush, 2007). Theglobal dissemination of MBL-producingP. aeruginosa strains has also reached theBalkan region (Lepsanovic et al., 2008;Sardelic et al., 2003). The objective of ourstudy was to detect and characterize P.aeruginosa isolates producing MBLs fromthe 400-bed paediatric tertiary carehospital Mother and Child Health Instituteof Serbia ‘Dr Vukan Cupic’",
publisher = "Soc General Microbiology, Reading",
journal = "Journal of Medical Microbiology",
title = "Emergence of VIM-2 metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates in a paediatric hospital in Serbia",
pages = "869-868",
number = "6",
volume = "60",
doi = "10.1099/jmm.0.029173-0"
}

Jovčić, B., Vasiljević, Z., Đukić, S., Topisirović, L.,& Kojić, M.. (2011). Emergence of VIM-2 metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates in a paediatric hospital in Serbia. in Journal of Medical Microbiology
Soc General Microbiology, Reading., 60(6), 868-869.
https://doi.org/10.1099/jmm.0.029173-0

Jovčić B, Vasiljević Z, Đukić S, Topisirović L, Kojić M. Emergence of VIM-2 metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates in a paediatric hospital in Serbia. in Journal of Medical Microbiology. 2011;60(6):868-869.
doi:10.1099/jmm.0.029173-0 .

Jovčić, Branko, Vasiljević, Zorica, Đukić, Slobodanka, Topisirović, Ljubiša, Kojić, Milan, "Emergence of VIM-2 metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates in a paediatric hospital in Serbia" in Journal of Medical Microbiology, 60, no. 6 (2011):868-869,
https://doi.org/10.1099/jmm.0.029173-0 . .