AdeABC efflux pump-mediated resistance to tigecycline in Acinetobacter baumannii isolates from Balkan hospitals
Аутори
Novović, KatarinaRadovanović, Milica
Milić, Vukašin
Gajić, Ina
Vasiljević, Zorica
Jovčić, Branko
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Introduction: Multidrug-resistant (MDR) Acinetobacter baumannii has been recognized as one of the
most serious healthcare challenges worldwide. Although tigecycline represents one of the last resort
therapies for MDR A. baumannii, resistance to this antibiotic has been reported and mostly is mediated
by AdeABC efflux pump. The aim of our study was to investigate the molecular mechanism responsible
for tigecycline resistance of thirty-seven A. baumannii isolates from Balkan medical settings (Serbia,
Bosnia and Herzegovina and Montenegro) gathered in 2016 and 2022.
Methods: Minimal inhibitory concentration (MIC) values for tigecycline were determined using microdilution method according to EUCAST guidelines. Inhibition of the efflux of tigecycline wastested by
the same method using a combination of antibiotic and efflux pump inhibitor (CCCP). Amino acid alternations within AdeS and AdeR proteins were detected by comparing to sequences of referent isolates
ATCC19606 and ATCC17978.... Expression of the adeB gene ofselected isolates was monitored by RT-qPCR.
Results: All tested isolates were resistant to tigecycline and showed significant decrease in tigecycline
MIC values in presence of CCCP (≥16-fold reduction) indicating that antibiotic efflux is responsible for
tigecycline resistance. The analysis of two-component system AdeRS, regulatory system of RND efflux
pump AdeABC, revealed that most of the isolates have G186V and N268H alternations in AdeS (n=32),
while most common changes in AdeR were V120I and A136V (n=29). In addition, RT-qPCR showed that
selected isolates upregulate expression of the adeB gene (from 1,13- to 3-fold).
Conclusion: This study revealed that AdeABC overexpression is the main mechanism of tigecycline resistance in A. baumannii isolated in Balkan hospitals.
Кључне речи:
Acinetobacter baumannii / tigecycline resistance / efflux pump / AdeABC / AdeRSИзвор:
CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia, 2023, 154-154Издавач:
- Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Novović, Katarina AU - Radovanović, Milica AU - Milić, Vukašin AU - Gajić, Ina AU - Vasiljević, Zorica AU - Jovčić, Branko PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2134 AB - Introduction: Multidrug-resistant (MDR) Acinetobacter baumannii has been recognized as one of the most serious healthcare challenges worldwide. Although tigecycline represents one of the last resort therapies for MDR A. baumannii, resistance to this antibiotic has been reported and mostly is mediated by AdeABC efflux pump. The aim of our study was to investigate the molecular mechanism responsible for tigecycline resistance of thirty-seven A. baumannii isolates from Balkan medical settings (Serbia, Bosnia and Herzegovina and Montenegro) gathered in 2016 and 2022. Methods: Minimal inhibitory concentration (MIC) values for tigecycline were determined using microdilution method according to EUCAST guidelines. Inhibition of the efflux of tigecycline wastested by the same method using a combination of antibiotic and efflux pump inhibitor (CCCP). Amino acid alternations within AdeS and AdeR proteins were detected by comparing to sequences of referent isolates ATCC19606 and ATCC17978. Expression of the adeB gene ofselected isolates was monitored by RT-qPCR. Results: All tested isolates were resistant to tigecycline and showed significant decrease in tigecycline MIC values in presence of CCCP (≥16-fold reduction) indicating that antibiotic efflux is responsible for tigecycline resistance. The analysis of two-component system AdeRS, regulatory system of RND efflux pump AdeABC, revealed that most of the isolates have G186V and N268H alternations in AdeS (n=32), while most common changes in AdeR were V120I and A136V (n=29). In addition, RT-qPCR showed that selected isolates upregulate expression of the adeB gene (from 1,13- to 3-fold). Conclusion: This study revealed that AdeABC overexpression is the main mechanism of tigecycline resistance in A. baumannii isolated in Balkan hospitals. 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 - AdeABC efflux pump-mediated resistance to tigecycline in Acinetobacter baumannii isolates from Balkan hospitals EP - 154 SP - 154 UR - https://hdl.handle.net/21.15107/rcub_imagine_2134 ER -
@conference{ author = "Novović, Katarina and Radovanović, Milica and Milić, Vukašin and Gajić, Ina and Vasiljević, Zorica and Jovčić, Branko", year = "2023", abstract = "Introduction: Multidrug-resistant (MDR) Acinetobacter baumannii has been recognized as one of the most serious healthcare challenges worldwide. Although tigecycline represents one of the last resort therapies for MDR A. baumannii, resistance to this antibiotic has been reported and mostly is mediated by AdeABC efflux pump. The aim of our study was to investigate the molecular mechanism responsible for tigecycline resistance of thirty-seven A. baumannii isolates from Balkan medical settings (Serbia, Bosnia and Herzegovina and Montenegro) gathered in 2016 and 2022. Methods: Minimal inhibitory concentration (MIC) values for tigecycline were determined using microdilution method according to EUCAST guidelines. Inhibition of the efflux of tigecycline wastested by the same method using a combination of antibiotic and efflux pump inhibitor (CCCP). Amino acid alternations within AdeS and AdeR proteins were detected by comparing to sequences of referent isolates ATCC19606 and ATCC17978. Expression of the adeB gene ofselected isolates was monitored by RT-qPCR. Results: All tested isolates were resistant to tigecycline and showed significant decrease in tigecycline MIC values in presence of CCCP (≥16-fold reduction) indicating that antibiotic efflux is responsible for tigecycline resistance. The analysis of two-component system AdeRS, regulatory system of RND efflux pump AdeABC, revealed that most of the isolates have G186V and N268H alternations in AdeS (n=32), while most common changes in AdeR were V120I and A136V (n=29). In addition, RT-qPCR showed that selected isolates upregulate expression of the adeB gene (from 1,13- to 3-fold). Conclusion: This study revealed that AdeABC overexpression is the main mechanism of tigecycline resistance in A. baumannii isolated in Balkan hospitals.", 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 = "AdeABC efflux pump-mediated resistance to tigecycline in Acinetobacter baumannii isolates from Balkan hospitals", pages = "154-154", url = "https://hdl.handle.net/21.15107/rcub_imagine_2134" }
Novović, K., Radovanović, M., Milić, V., Gajić, I., Vasiljević, Z.,& Jovčić, B.. (2023). AdeABC efflux pump-mediated resistance to tigecycline in Acinetobacter baumannii isolates from Balkan hospitals. 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., 154-154. https://hdl.handle.net/21.15107/rcub_imagine_2134
Novović K, Radovanović M, Milić V, Gajić I, Vasiljević Z, Jovčić B. AdeABC efflux pump-mediated resistance to tigecycline in Acinetobacter baumannii isolates from Balkan hospitals. 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;:154-154. https://hdl.handle.net/21.15107/rcub_imagine_2134 .
Novović, Katarina, Radovanović, Milica, Milić, Vukašin, Gajić, Ina, Vasiljević, Zorica, Jovčić, Branko, "AdeABC efflux pump-mediated resistance to tigecycline in Acinetobacter baumannii isolates from Balkan hospitals" 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):154-154, https://hdl.handle.net/21.15107/rcub_imagine_2134 .