Over expression of AdeABC and AcrAB-TolC efflux systems confers tigecycline resistance in clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae

Yin, Yue-Ping; Ziyun, Yue; Zhang, Yongbo; Li, Fuqiang; Zhang, Qinghua

doi:10.1590/0037-8682-0411-2015

Cited by 26 publications

(21 citation statements)

References 25 publications

(29 reference statements)

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“…Notably, in our research, the presence of Acr AB- Tol C and mdt K genes were strongly associated with MDR K. pneumoniae patterns. These results are consistent with other previous studies, that demonstrated that the multidrug efflux pump system ( Acr AB -Tol C) in K. pneumoniae was responsible for resistance to quinolones, tetracyclines, TGC, and beta-lactams in various MDR isolates (Padilla et al, 2010; Yuhan et al, 2016).…”

Section: Discussionsupporting

confidence: 93%

High Prevalence of Multidrug-Resistant Klebsiella pneumoniae Harboring Several Virulence and β-Lactamase Encoding Genes in a Brazilian Intensive Care Unit

et al. 2019

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Klebsiella pneumoniae is an important opportunistic pathogen that commonly causes nosocomial infections and contributes to substantial morbidity and mortality. We sought to investigate the antibiotic resistance profile, pathogenic potential and the clonal relationships between K. pneumoniae (n = 25) isolated from patients and sources at a tertiary care hospital’s intensive care units (ICUs) in the northern region of Brazil. Most of K. pneumoniae isolates (n = 21, 84%) were classified as multidrug resistant (MDR) with high-level resistance to β-lactams, aminoglycosides, quinolones, tigecycline, and colistin. All the 25 isolates presented extended-spectrum beta-lactamase-producing (ESBL), including carbapenemase producers, and carried the blaKPC (100%), blaTEM (100%), blaSHV variants (n = 24, 96%), blaOXA-1 group (n = 21, 84%) and blaCTX-M-1 group (n = 18, 72%) genes. The K2 serotype was found in 4% (n = 1) of the isolates, and the K1 was not detected. The virulence-associated genes found among the 25 isolates were mrkD (n = 24, 96%), fimH-1 (n = 22, 88%), entB (100%), iutA (n = 10, 40%), ybtS (n = 15, 60%). The genes related with efflux pumps and outer membrane porins found were AcrAB (100%), tolC (n = 24, 96%), mdtK (n = 22, 88%), OmpK35 (n = 15, 60%), and OmpK36 (n = 7, 28%). ERIC-PCR was employed to determine the clonal relationship between the different isolated strains. The obtained ERIC-PCR patterns revealed that the similarity between isolates was above 70%. To determine the sequence types (STs) a multilocus sequence typing (MLST) assay was used. The results indicated the presence of high-risk international clones among the isolates. In our study, the wide variety of MDR K. pneumoniae harboring β-lactams and virulence genes strongly suggest a necessity for the implementation of effective strategies to prevent and control the spread of antibiotic resistant infections.

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Section: Discussionsupporting

confidence: 93%

High Prevalence of Multidrug-Resistant Klebsiella pneumoniae Harboring Several Virulence and β-Lactamase Encoding Genes in a Brazilian Intensive Care Unit

et al. 2019

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“…Gene disruption analysis proved that RND pumps can eject tetracyclines, elevating MICs for tigecyline, minocycline, and tetracycline [182]. Other RND pumps like AdeIJK exist but may play a less profound role on tetracycline efflux and can be synergistic with AdeABC [183].…”

Section: Tetracyclines and Glycylcyclinesmentioning

confidence: 99%

“…Efflux pump overactivity RND pump AdeABC, AdeIJK, and AcrAB-TolC [179][180][181][182][183][184][185] Tet pump TetA and TetB [180] Ribosomal protection Tetracycline dissociation from ribosome Tet(O) and Tet(M) [180,[186][187][188] Fluoroquinolones Target mutation DNA gyrase GyrA [191,192] DNA topoisomerase IV ParC [191,192] Efflux pump overactivity RND pump AdeABC [81,191] MATE family AbeM [194] Aminoglycosides Drug inactivating enzymes Aminoglycoside modifying enzymes AAC(3)-Ia [185] AAC(3 )-Ia [200] ANT(2 )-Ia [200] ANT(3")-Ia [199] Target mutation 16sRNA methylase genes armA, rmtA, rmtB, rmtC, and rmtD [197,201] Efflux pump overactivity RND pumps AdeABC [175,202] Macrolides Efflux pump overactivity SMR pump AbeS [204] Polymyxins…”

Section: Tertacyclinesmentioning

confidence: 99%

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

2020

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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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“…We found that the AcrAB-TolC efflux pump system was highly expressed in group B, indicating that this system plays an essential role in the development of CRKP resistance to tigecycline. The AcrAB-TolC efflux pump is involved in resistancenodulation cell division and has been reported to be resistant to several types of antibiotics (Zhong et al, 2014;Castanheira et al, 2016;Yuhan et al, 2016). However, Nielsen et al (2014) reported that the IS5 insertion element increased the MIC of tigecycline by four-fold and was not dependent on the functional AcrAB-TolC efflux pump, suggesting that the AcrAB-TolC efflux pump is not the only mechanism causing tigecycline resistance.…”

Section: Discussionmentioning

confidence: 99%

CusS-CusR Two-Component System Mediates Tigecycline Resistance in Carbapenem-Resistant Klebsiella pneumoniae

et al. 2020

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Background: The increase in carbapenem-resistant Klebsiella pneumoniae (CRKP), especially the emergence of tigecycline-resistant K. pneumoniae (KP), is a serious public health concern. However, the underlying mechanism of tigecycline resistance is unclear. In this study, we evaluated the role of the CusS-CusR two-component system (TCS), which is associated with copper/silver resistance, in tigecycline resistance in CRKP. Methods: Following the in vitro evolution of tigecycline-resistant KP, the minimum inhibitory concentrations of tigecycline were determined using the micro-broth dilution method. RNA sequencing and data analysis were performed to identify differentially expressed genes. Quantitative PCR (qPCR) was performed to verify the genes of interest. Genes associated with tigecycline resistance, such as ramR, tex (T), and tet (A), were detected by PCR, and then mutants were confirmed by sequencing. Additionally, the efflux pump-associated genes soxS, oqxA, oqxB, acrE, and acrF were also analyzed by qPCR. CusR was deleted and complemented by the suicide vector pKO3-Km plasmid and pGEM-T-easy plasmid, respectively. Results: Nine strains of KP were evaluated in our study. Strains A2 and A3 were evolved from A1, B2, and B3 were evolved from B1, and C2 and C3 were evolved from C1. The tigecycline minimum inhibitory concentration for A1, B1, and C1 was 0.5 µg/mL; that for A2, B2, and C3 was 16.0 µg/mL; and that for A3, B3, and C3 was 32.0 µg/mL. RNAsequencing and qPCR confirmed that the differentially expressed genes cusE, cusS, cusR, cusC, cusF, cusB, and cusA showed higher expression in C2 and C3 than in C1. Genes related to the efflux pump AcrAB-TolC showed higher expression in B2 and B3 than in B1. No mutants of ramR, tex (T), or tet (A) were detected. SoxS, oqxA, oqxB, acrE, and acrF did not show increased expression in any group. After deletion and

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Over expression of AdeABC and AcrAB-TolC efflux systems confers tigecycline resistance in clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae

Cited by 26 publications

References 25 publications

High Prevalence of Multidrug-Resistant Klebsiella pneumoniae Harboring Several Virulence and β-Lactamase Encoding Genes in a Brazilian Intensive Care Unit

High Prevalence of Multidrug-Resistant Klebsiella pneumoniae Harboring Several Virulence and β-Lactamase Encoding Genes in a Brazilian Intensive Care Unit

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

CusS-CusR Two-Component System Mediates Tigecycline Resistance in Carbapenem-Resistant Klebsiella pneumoniae

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