TY  - 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 .