Efflux-Related Carbapenem Resistance in <i>Acinetobacter baumannii</i> Is Associated with Two-Component Regulatory Efflux Systems’ Alteration and Insertion of ΔAbaR25-Type Island Fragment
The efflux pumps, beside the class D carbapenem-hydrolysing enzymes (CHLDs), are being increasingly investigated as a mechanism of carbapenem resistance in <i>Acinetobacter baumannii</i>. This study investigates the contribution of efflux mechanism to carbapenem resistance in 61 acquired...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/11/9525 |
| _version_ | 1797597433496076288 |
|---|---|
| author | Alicja Słoczyńska Matthew E. Wand Lucy J. Bock Stefan Tyski Agnieszka E. Laudy |
| author_facet | Alicja Słoczyńska Matthew E. Wand Lucy J. Bock Stefan Tyski Agnieszka E. Laudy |
| author_sort | Alicja Słoczyńska |
| collection | DOAJ |
| description | The efflux pumps, beside the class D carbapenem-hydrolysing enzymes (CHLDs), are being increasingly investigated as a mechanism of carbapenem resistance in <i>Acinetobacter baumannii</i>. This study investigates the contribution of efflux mechanism to carbapenem resistance in 61 acquired <i>bla</i><sub>CHDL</sub>-genes-carrying <i>A. baumannii</i> clinical strains isolated in Warsaw, Poland. Studies were conducted using phenotypic (susceptibility testing to carbapenems ± efflux pump inhibitors (EPIs)) and molecular (determining expression levels of efflux operon with regulatory-gene and whole genome sequencing (WGS)) methods. EPIs reduced carbapenem resistance of 14/61 isolates. Upregulation (5–67-fold) of <i>adeB</i> was observed together with mutations in the sequences of AdeRS local and of BaeS global regulators in all 15 selected isolates. Long-read WGS of isolate no. AB96 revealed the presence of AbaR25 resistance island and its two disrupted elements: the first contained a duplicate IS<i>Aba1-bla</i><sub>OXA-23</sub>, and the second was located between <i>adeR</i> and <i>adeA</i> in the efflux operon. This insert was flanked by two copies of IS<i>Aba1</i>, and one of them provides a strong promoter for <i>adeABC</i>, elevating the <i>adeB</i> expression levels. Our study for the first time reports the involvement of the insertion of the ΔAbaR25-type resistance island fragment with IS<i>Aba1</i> element upstream the efflux operon in the carbapenem resistance of <i>A. baumannii</i>. |
| first_indexed | 2024-03-11T03:06:00Z |
| format | Article |
| id | doaj.art-c85f5f1d77fa43eb894b4e1c67f9e60a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:06:00Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c85f5f1d77fa43eb894b4e1c67f9e60a2023-11-18T08:00:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411952510.3390/ijms24119525Efflux-Related Carbapenem Resistance in <i>Acinetobacter baumannii</i> Is Associated with Two-Component Regulatory Efflux Systems’ Alteration and Insertion of ΔAbaR25-Type Island FragmentAlicja Słoczyńska0Matthew E. Wand1Lucy J. Bock2Stefan Tyski3Agnieszka E. Laudy4Department of Pharmaceutical Microbiology and Bioanalysis, Medical University of Warsaw, 02-097 Warsaw, PolandUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UKUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UKDepartment of Antibiotics and Microbiology, National Medicines Institute, 00-725 Warsaw, PolandDepartment of Pharmaceutical Microbiology and Bioanalysis, Medical University of Warsaw, 02-097 Warsaw, PolandThe efflux pumps, beside the class D carbapenem-hydrolysing enzymes (CHLDs), are being increasingly investigated as a mechanism of carbapenem resistance in <i>Acinetobacter baumannii</i>. This study investigates the contribution of efflux mechanism to carbapenem resistance in 61 acquired <i>bla</i><sub>CHDL</sub>-genes-carrying <i>A. baumannii</i> clinical strains isolated in Warsaw, Poland. Studies were conducted using phenotypic (susceptibility testing to carbapenems ± efflux pump inhibitors (EPIs)) and molecular (determining expression levels of efflux operon with regulatory-gene and whole genome sequencing (WGS)) methods. EPIs reduced carbapenem resistance of 14/61 isolates. Upregulation (5–67-fold) of <i>adeB</i> was observed together with mutations in the sequences of AdeRS local and of BaeS global regulators in all 15 selected isolates. Long-read WGS of isolate no. AB96 revealed the presence of AbaR25 resistance island and its two disrupted elements: the first contained a duplicate IS<i>Aba1-bla</i><sub>OXA-23</sub>, and the second was located between <i>adeR</i> and <i>adeA</i> in the efflux operon. This insert was flanked by two copies of IS<i>Aba1</i>, and one of them provides a strong promoter for <i>adeABC</i>, elevating the <i>adeB</i> expression levels. Our study for the first time reports the involvement of the insertion of the ΔAbaR25-type resistance island fragment with IS<i>Aba1</i> element upstream the efflux operon in the carbapenem resistance of <i>A. baumannii</i>.https://www.mdpi.com/1422-0067/24/11/9525multidrug resistancecarbapenem resistanceefflux pumpinsertion sequenceresistance islandEPI |
| spellingShingle | Alicja Słoczyńska Matthew E. Wand Lucy J. Bock Stefan Tyski Agnieszka E. Laudy Efflux-Related Carbapenem Resistance in <i>Acinetobacter baumannii</i> Is Associated with Two-Component Regulatory Efflux Systems’ Alteration and Insertion of ΔAbaR25-Type Island Fragment International Journal of Molecular Sciences multidrug resistance carbapenem resistance efflux pump insertion sequence resistance island EPI |
| title | Efflux-Related Carbapenem Resistance in <i>Acinetobacter baumannii</i> Is Associated with Two-Component Regulatory Efflux Systems’ Alteration and Insertion of ΔAbaR25-Type Island Fragment |
| title_full | Efflux-Related Carbapenem Resistance in <i>Acinetobacter baumannii</i> Is Associated with Two-Component Regulatory Efflux Systems’ Alteration and Insertion of ΔAbaR25-Type Island Fragment |
| title_fullStr | Efflux-Related Carbapenem Resistance in <i>Acinetobacter baumannii</i> Is Associated with Two-Component Regulatory Efflux Systems’ Alteration and Insertion of ΔAbaR25-Type Island Fragment |
| title_full_unstemmed | Efflux-Related Carbapenem Resistance in <i>Acinetobacter baumannii</i> Is Associated with Two-Component Regulatory Efflux Systems’ Alteration and Insertion of ΔAbaR25-Type Island Fragment |
| title_short | Efflux-Related Carbapenem Resistance in <i>Acinetobacter baumannii</i> Is Associated with Two-Component Regulatory Efflux Systems’ Alteration and Insertion of ΔAbaR25-Type Island Fragment |
| title_sort | efflux related carbapenem resistance in i acinetobacter baumannii i is associated with two component regulatory efflux systems alteration and insertion of δabar25 type island fragment |
| topic | multidrug resistance carbapenem resistance efflux pump insertion sequence resistance island EPI |
| url | https://www.mdpi.com/1422-0067/24/11/9525 |
| work_keys_str_mv | AT alicjasłoczynska effluxrelatedcarbapenemresistanceiniacinetobacterbaumanniiiisassociatedwithtwocomponentregulatoryeffluxsystemsalterationandinsertionofdabar25typeislandfragment AT matthewewand effluxrelatedcarbapenemresistanceiniacinetobacterbaumanniiiisassociatedwithtwocomponentregulatoryeffluxsystemsalterationandinsertionofdabar25typeislandfragment AT lucyjbock effluxrelatedcarbapenemresistanceiniacinetobacterbaumanniiiisassociatedwithtwocomponentregulatoryeffluxsystemsalterationandinsertionofdabar25typeislandfragment AT stefantyski effluxrelatedcarbapenemresistanceiniacinetobacterbaumanniiiisassociatedwithtwocomponentregulatoryeffluxsystemsalterationandinsertionofdabar25typeislandfragment AT agnieszkaelaudy effluxrelatedcarbapenemresistanceiniacinetobacterbaumanniiiisassociatedwithtwocomponentregulatoryeffluxsystemsalterationandinsertionofdabar25typeislandfragment |