@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"
}
