THE ROLE OF EFFLUX PUMPS IN TIGECYCLINE RESISTANCE OF ACINETOBACTER BAUMANNII ISOLATES FROM WESTERN BALKAN HOSPITALS
Аутори
Šapić, KatarinaNovović, Katarina
Radovanović, Milica
Gajić, Ina
Vasiljević, Zorica
Malešević, Milka
Jovčić, Branko
Остала ауторства
Dimkić, IvicaKekić, Dušan
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The increasing prevalence of multidrug-resistant
(MDR) Acinetobacter baumannii limits effective
therapeutic options, and tigecycline has been
considered one of the last resort therapies for
MDR A. baumannii infections. Nevertheless, A.
baumannii isolates resistant to tigecycline are
becoming increasingly reported, mostly due to
overexpression of efflux pumps. The three major
RND efflux systems conferring tigecycline resistance
in A. baumannii are AdeABC, AdeFGH, and
AdeIJK, and their expression is regulated by the
two-component system AdeRS, the LysR-type
regulator AdeL, and the TetR-type regulator AdeN,
respectively. Following the above, we aimed
to determine the role of efflux pumps in tigecycline
resistance of thirty-seven A. baumannii isolates
collected from Western Balkan healthcare
settings (Serbia, Bosnia and Herzegovina and
Montenegro) in 2016 and 2022. The majority of
isolates belonged to the most prevalent international
clonal lineage IC2 (n = 32), four is...olates are
members of IC1, while only one isolate is identified
as IC3. All tested isolates demonstrated a
significant decrease in tigecycline MIC in presence
of efflux pump inhibitor CCCP (≥16-fold reduction)
indicating that mechanism responsible
for tigecycline resistance is antibiotic efflux. The
comparison of target efflux pump regulatory
proteins, translated from nucleotide sequences,
to reference strains ATCC19606 and ATCC17978
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) as described in previous studies.
Substitution Q262R was detected exclusively in
AdeL proteins of IC1 isolates, while no mutations
were observed within AdeN regulators. Expression
of the adeB, adeG, and adeJ genes in six selected
isolates was upregulated in four (1,4- to
3-fold), six (1,6- to 2,6-fold), and three isolates
(1,7- to 4-fold), respectively. This study confirmed
that overexpression of efflux pump encoding
genes enables tigecycline resistance in clinical
A. baumannii isolates.
Кључне речи:
Acinetobacter baumannii / RND efflux pumps / tigecycline resistance / AdeABC / AdeFGHИзвор:
XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health, 2024, 187-187Издавач:
- Serbian Society for Microbiology
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)
Напомена:
- Book of abstract: From biotechnology to human and planetary health XIII congress of microbiologists of Serbia with international participation Mikromed regio 5, ums series 24: 4th – 6th april 2024, Mona Plaza hotel, Belgrade, Serbia
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Šapić, Katarina AU - Novović, Katarina AU - Radovanović, Milica AU - Gajić, Ina AU - Vasiljević, Zorica AU - Malešević, Milka AU - Jovčić, Branko PY - 2024 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2386 AB - The increasing prevalence of multidrug-resistant (MDR) Acinetobacter baumannii limits effective therapeutic options, and tigecycline has been considered one of the last resort therapies for MDR A. baumannii infections. Nevertheless, A. baumannii isolates resistant to tigecycline are becoming increasingly reported, mostly due to overexpression of efflux pumps. The three major RND efflux systems conferring tigecycline resistance in A. baumannii are AdeABC, AdeFGH, and AdeIJK, and their expression is regulated by the two-component system AdeRS, the LysR-type regulator AdeL, and the TetR-type regulator AdeN, respectively. Following the above, we aimed to determine the role of efflux pumps in tigecycline resistance of thirty-seven A. baumannii isolates collected from Western Balkan healthcare settings (Serbia, Bosnia and Herzegovina and Montenegro) in 2016 and 2022. The majority of isolates belonged to the most prevalent international clonal lineage IC2 (n = 32), four isolates are members of IC1, while only one isolate is identified as IC3. All tested isolates demonstrated a significant decrease in tigecycline MIC in presence of efflux pump inhibitor CCCP (≥16-fold reduction) indicating that mechanism responsible for tigecycline resistance is antibiotic efflux. The comparison of target efflux pump regulatory proteins, translated from nucleotide sequences, to reference strains ATCC19606 and ATCC17978 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) as described in previous studies. Substitution Q262R was detected exclusively in AdeL proteins of IC1 isolates, while no mutations were observed within AdeN regulators. Expression of the adeB, adeG, and adeJ genes in six selected isolates was upregulated in four (1,4- to 3-fold), six (1,6- to 2,6-fold), and three isolates (1,7- to 4-fold), respectively. This study confirmed that overexpression of efflux pump encoding genes enables tigecycline resistance in clinical A. baumannii isolates. PB - Serbian Society for Microbiology C3 - XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health T1 - THE ROLE OF EFFLUX PUMPS IN TIGECYCLINE RESISTANCE OF ACINETOBACTER BAUMANNII ISOLATES FROM WESTERN BALKAN HOSPITALS EP - 187 SP - 187 UR - https://hdl.handle.net/21.15107/rcub_imagine_2386 ER -
@conference{ author = "Šapić, Katarina and Novović, Katarina and Radovanović, Milica and Gajić, Ina and Vasiljević, Zorica and Malešević, Milka and Jovčić, Branko", year = "2024", abstract = "The increasing prevalence of multidrug-resistant (MDR) Acinetobacter baumannii limits effective therapeutic options, and tigecycline has been considered one of the last resort therapies for MDR A. baumannii infections. Nevertheless, A. baumannii isolates resistant to tigecycline are becoming increasingly reported, mostly due to overexpression of efflux pumps. The three major RND efflux systems conferring tigecycline resistance in A. baumannii are AdeABC, AdeFGH, and AdeIJK, and their expression is regulated by the two-component system AdeRS, the LysR-type regulator AdeL, and the TetR-type regulator AdeN, respectively. Following the above, we aimed to determine the role of efflux pumps in tigecycline resistance of thirty-seven A. baumannii isolates collected from Western Balkan healthcare settings (Serbia, Bosnia and Herzegovina and Montenegro) in 2016 and 2022. The majority of isolates belonged to the most prevalent international clonal lineage IC2 (n = 32), four isolates are members of IC1, while only one isolate is identified as IC3. All tested isolates demonstrated a significant decrease in tigecycline MIC in presence of efflux pump inhibitor CCCP (≥16-fold reduction) indicating that mechanism responsible for tigecycline resistance is antibiotic efflux. The comparison of target efflux pump regulatory proteins, translated from nucleotide sequences, to reference strains ATCC19606 and ATCC17978 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) as described in previous studies. Substitution Q262R was detected exclusively in AdeL proteins of IC1 isolates, while no mutations were observed within AdeN regulators. Expression of the adeB, adeG, and adeJ genes in six selected isolates was upregulated in four (1,4- to 3-fold), six (1,6- to 2,6-fold), and three isolates (1,7- to 4-fold), respectively. This study confirmed that overexpression of efflux pump encoding genes enables tigecycline resistance in clinical A. baumannii isolates.", publisher = "Serbian Society for Microbiology", journal = "XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health", title = "THE ROLE OF EFFLUX PUMPS IN TIGECYCLINE RESISTANCE OF ACINETOBACTER BAUMANNII ISOLATES FROM WESTERN BALKAN HOSPITALS", pages = "187-187", url = "https://hdl.handle.net/21.15107/rcub_imagine_2386" }
Šapić, K., Novović, K., Radovanović, M., Gajić, I., Vasiljević, Z., Malešević, M.,& Jovčić, B.. (2024). THE ROLE OF EFFLUX PUMPS IN TIGECYCLINE RESISTANCE OF ACINETOBACTER BAUMANNII ISOLATES FROM WESTERN BALKAN HOSPITALS. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health Serbian Society for Microbiology., 187-187. https://hdl.handle.net/21.15107/rcub_imagine_2386
Šapić K, Novović K, Radovanović M, Gajić I, Vasiljević Z, Malešević M, Jovčić B. THE ROLE OF EFFLUX PUMPS IN TIGECYCLINE RESISTANCE OF ACINETOBACTER BAUMANNII ISOLATES FROM WESTERN BALKAN HOSPITALS. in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health. 2024;:187-187. https://hdl.handle.net/21.15107/rcub_imagine_2386 .
Šapić, Katarina, Novović, Katarina, Radovanović, Milica, Gajić, Ina, Vasiljević, Zorica, Malešević, Milka, Jovčić, Branko, "THE ROLE OF EFFLUX PUMPS IN TIGECYCLINE RESISTANCE OF ACINETOBACTER BAUMANNII ISOLATES FROM WESTERN BALKAN HOSPITALS" in XIII Congress of microbiologists of Serbia: From biotechnology to human and planetary health (2024):187-187, https://hdl.handle.net/21.15107/rcub_imagine_2386 .