Relationship between AdeABC Efflux Pump Genes and Carbapenem in Multidrug-resistant Acinetobacter baumannii

ABSTRACTAcinetobacter baumanniihas emerged as an important multidrug-resistant nosocomial pathogen. In previous work, we identified a putative MFS transporter, AU097_RS17040, involved in the pathogenicity ofA. baumannii(M. Pérez-Varela, J. Corral, J. A. Vallejo, S. Rumbo-Feal, G. Bou, J. Aranda, and J. Barbé, Infect Immun 85:e00327-17, 2017,https://doi.org/10.1128/IAI.00327-17). In this study, we analyzed the susceptibility to diverse antimicrobial agents ofA. baumanniicells defective in this transporter, referred to as AbaQ. Our results showed that AbaQ is mainly involved in the extrusion of quinolone-type drugs inA. baumannii.

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Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

Antibiotics ◽

10.3390/antibiotics9030119 ◽

2020 ◽

Vol 9 (3) ◽

pp. 119 ◽

Cited By ~ 12

Author(s):

Carole Ayoub Moubareck ◽

Dalal Hammoudi Halat

Keyword(s):

Acinetobacter Baumannii ◽

Virulence Factors ◽

Efflux Pump ◽

Iron Acquisition ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Biofilm Production ◽

Resistant Phenotype ◽

Severe Infections ◽

Hydrolyzing Enzymes

Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. Pathogenesis in A. baumannii infections is an outcome of multiple virulence factors, including porins, capsules, and cell wall lipopolysaccharide, enzymes, biofilm production, motility, and iron-acquisition systems, among others. Such virulence factors help the organism to resist stressful environmental conditions and enable development of severe infections. Parallel to increased prevalence of infections caused by A. baumannii, challenging and diverse resistance mechanisms in this pathogen are well recognized, with major classes of antibiotics becoming minimally effective. Through a wide array of antibiotic-hydrolyzing enzymes, efflux pump changes, impermeability, and antibiotic target mutations, A. baumannii models a unique ability to maintain a multidrug-resistant phenotype, further complicating treatment. Understanding mechanisms behind diseases, virulence, and resistance acquisition are central to infectious disease knowledge about A. baumannii. The aims of this review are to highlight infections and disease-producing factors in A. baumannii and to touch base on mechanisms of resistance to various antibiotic classes.

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Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

Folia Histochemica et Cytobiologica ◽

10.2478/v10042-008-0056-x ◽

2008 ◽

Vol 46 (3) ◽

Cited By ~ 54

Author(s):

Piotr Wieczorek ◽

Paweł Sacha ◽

Tomasz Hauschild ◽

Marcin Zórawski ◽

Małgorzata Krawczyk ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Efflux Pump ◽

Multidrug Resistant ◽

Resistance To Antibiotics

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Insights into the Resistome and Phylogenomics of a ST195 Multidrug-Resistant Acinetobacter baumannii Clinical Isolate from the Czech Republic

Life ◽

10.3390/life11101079 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1079

Author(s):

Patrik Mlynarcik ◽

Monika Dolejska ◽

Iva Vagnerova ◽

Jana Petrzelova ◽

Iva Sukkar ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Clinical Isolate ◽

Efflux Pump ◽

Resistance Mechanism ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Clinical Settings ◽

Sequencing Analysis ◽

Pump System ◽

The Czech Republic

Increasing antimicrobial resistance in nosocomial pathogens, such as Acinetobacter baumannii, is becoming a serious threat to public health. It is necessary to detect β-lactamase-producing microorganisms in clinical settings to be able to control the spread of carbapenem resistance. This study was conducted to evaluate the presence of β-lactamases in a selected clinical isolate of A. baumannii of ST2P/ST195Ox and to characterize possible enzymes, as well as its β-lactam resistome, using PCR and whole-genome sequencing analysis. PCR and sequencing confirmed that the isolate harbored five bla gene alleles, namely, blaADC-73, blaTEM-1, blaOXA-23, blaOXA-58 and blaOXA-66, as well as aminoglycosides, macrolides, sulfonamides and tetracyclines resistance determinants, which were either chromosomally and/or plasmid located. Furthermore, a gene order comparison using MAUVE alignment showed multiple changes compared with the clinical isolate of Malaysian A. baumannii AC30 genome and 76 regions with high homology. This study suggests that resistance to β-lactams in this A. baumannii isolate is mainly due to an overproduction of β-lactamases in combination with other resistance mechanism (efflux pump system).

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In vitro synergistic effect of amlodipine and imipenem on the expression of the AdeABC efflux pump in multidrug-resistant Acinetobacter baumannii

PLoS ONE ◽

10.1371/journal.pone.0198061 ◽

2018 ◽

Vol 13 (6) ◽

pp. e0198061 ◽

Cited By ~ 2

Author(s):

Chao Hu ◽

Yujun Li ◽

Ziwen Zhao ◽

Shuquan Wei ◽

Zhuxiang Zhao ◽

...

Keyword(s):

Synergistic Effect ◽

Acinetobacter Baumannii ◽

Efflux Pump ◽

Multidrug Resistant

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Whole genome analysis of extensively drug-resistant Acinetobacter bau-mannii clinical isolates in Thailand

Infectious Disorders - Drug Targets ◽

10.2174/1871526520999201116201911 ◽

2020 ◽

Vol 20 ◽

Author(s):

Peechanika Chopjitt ◽

Anusak Kerdsin ◽

Dan Takeuchi ◽

Rujirat Hatrongjit ◽

Parichart Boueroy ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Acinetobacter Baumannii ◽

Genome Sequencing ◽

Efflux Pump ◽

Multidrug Resistant ◽

Whole Genome ◽

Drug Resistant ◽

Resistant Genes ◽

Extensively Drug Resistant ◽

Antibiotic Efflux

Background:: Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen and caus-ing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase understanding of resistant mechanisms, the emergence of novel re-sistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients. Objective:: This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand. Methods:: Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted. Results:: Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial-resistant genes—ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 -lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminogly-coside-resistant genes (armA, aph(3')-Ia, aph(3'')-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfon-amide-resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates. Conclusions:: Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under interna-tional clone II with difference STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimi-crobial agents. Inactivation of antimicrobials and target modification by enzymes, and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

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Distribution of different efflux pump genes in clinical isolates of multidrug-resistant Acinetobacter baumannii and their correlation with antimicrobial resistance

Journal of Microbiology Immunology and Infection ◽

10.1016/j.jmii.2015.04.004 ◽

2017 ◽

Vol 50 (2) ◽

pp. 224-231 ◽

Cited By ~ 26

Author(s):

Ming-Feng Lin ◽

Yun-You Lin ◽

Chi-Chao Tu ◽

Chung-Yu Lan

Keyword(s):

Antimicrobial Resistance ◽

Acinetobacter Baumannii ◽

Efflux Pump ◽

Multidrug Resistant ◽

Clinical Isolates

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First Identification and Characterization of an AdeABC-Like Efflux Pump inAcinetobacterGenomospecies 13TU

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01142-10 ◽

2011 ◽

Vol 55 (3) ◽

pp. 1285-1286 ◽

Cited By ~ 12

Author(s):

Ignasi Roca ◽

Paula Espinal ◽

Sara Martí ◽

Jordi Vila

Keyword(s):

Multidrug Resistance ◽

Acinetobacter Baumannii ◽

Clinical Isolate ◽

Nosocomial Infections ◽

Efflux Pump ◽

Hospital Setting ◽

Multidrug Resistant ◽

Identification Techniques ◽

Identification And Characterization

ABSTRACTNon-Acinetobacter baumanniispp. are emerging among clinicalAcinetobacterisolates causing nosocomial infections, and some (such as genomospecies 13TU) appear to be multidrug resistant. The prevalence of non-Acinetobacter baumanniispp. in the hospital setting is likely understated due to poor identification techniques. We report the first identification of an AdeABC-type efflux pump in anAcinetobactergenomospecies 13TU clinical isolate, its contribution to multidrug resistance, and the coexistence of three Ade-type efflux pumps in this strain.

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