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

Life ◽  
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).

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

2011 ◽  
Vol 55 (3) ◽  
pp. 1285-1286 ◽  
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.

scholarly journals RND-Type Efflux Pumps in Multidrug-Resistant Clinical Isolates of Acinetobacter baumannii: Major Role for AdeABC Overexpression and AdeRS Mutations

2013 ◽  
Vol 57 (7) ◽  
pp. 2989-2995 ◽  
Author(s):  
Eun-Jeong Yoon ◽  
Patrice Courvalin ◽  
Catherine Grillot-Courvalin
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Regulatory System ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Clinical Settings ◽  
Two Component System ◽  
Content Type ◽  
High Incidence ◽  
Two Component

ABSTRACTIncreased expression of chromosomal genes for resistance-nodulation-cell division (RND)-type efflux systems plays a major role in the multidrug resistance (MDR) ofAcinetobacter baumannii. However, the relative contributions of the three most prevalent pumps, AdeABC, AdeFGH, and AdeIJK, have not been evaluated in clinical settings. We have screened 14 MDR clinical isolates shown to be distinct on the basis of multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) for the presence and overexpression of the three Ade efflux systems and analyzed the sequences of the regulators AdeRS, a two-component system, for AdeABC and AdeL, a LysR-type regulator, for AdeFGH. GeneadeBwas detected in 13 of 14 isolates, andadeGand the intrinsicadeJgene were detected in all strains. Significant overexpression ofadeBwas observed in 10 strains, whereas only 7 had moderately increased levels of expression of AdeFGH, and none overexpressed AdeIJK. Thirteen strains had reduced susceptibility to tigecycline, but there was no correlation between tigecycline MICs and the levels of AdeABC expression, suggesting the presence of other mechanisms for tigecycline resistance. No mutations were found in the highly conserved LysR regulator of the nine strains expressing AdeFGH. In contrast, functional mutations were found in conserved domains of AdeRS in all the strains that overexpressed AdeABC with two mutational hot spots, one in AdeS near histidine 149 suggesting convergent evolution and the other in the DNA binding domain of AdeR compatible with horizontal gene transfer. This report outlines the high incidence of AdeABC efflux pump overexpression in MDRA. baumanniias a result of a variety of single mutations in the corresponding two-component regulatory system.

scholarly journals Binding of Tetracyclines to Acinetobacter baumannii TetR Involves Two Arginines as Specificity Determinants

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuela Sumyk ◽  
Stephanie Himpich ◽  
Wuen Ee Foong ◽  
Andrea Herrmann ◽  
Klaas M. Pos ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Binding Pocket ◽  
Multidrug Resistant ◽  
Tetracycline Antibiotics ◽  
Binding Preference ◽  
Binding Data ◽  
Tetr Repressor ◽  
Specificity Determinants

Acinetobacter baumannii is an important nosocomial pathogen that requires thoughtful consideration in the antibiotic prescription strategy due to its multidrug resistant phenotype. Tetracycline antibiotics have recently been re-administered as part of the combination antimicrobial regimens to treat infections caused by A. baumannii. We show that the TetA(G) efflux pump of A. baumannii AYE confers resistance to a variety of tetracyclines including the clinically important antibiotics doxycycline and minocycline, but not to tigecycline. Expression of tetA(G) gene is regulated by the TetR repressor of A. baumannii AYE (AbTetR). Thermal shift binding experiments revealed that AbTetR preferentially binds tetracyclines which carry a O-5H moiety in ring B, whereas tetracyclines with a 7-dimethylamino moiety in ring D are less well-recognized by AbTetR. Confoundingly, tigecycline binds to AbTetR even though it is not transported by TetA(G) efflux pump. Structural analysis of the minocycline-bound AbTetR-Gln116Ala variant suggested that the non-conserved Arg135 interacts with the ring D of minocycline by cation-π interaction, while the invariant Arg104 engages in H-bonding with the O-11H of minocycline. Interestingly, the Arg135Ala variant exhibited a binding preference for tetracyclines with an unmodified ring D. In contrast, the Arg104Ala variant preferred to bind tetracyclines which carry a O-6H moiety in ring C except for tigecycline. We propose that Arg104 and Arg135, which are embedded at the entrance of the AbTetR binding pocket, play important roles in the recognition of tetracyclines, and act as a barrier to prevent the release of tetracycline from its binding pocket upon AbTetR activation. The binding data and crystal structures obtained in this study might provide further insight for the development of new tetracycline antibiotics to evade the specific efflux resistance mechanism deployed by A. baumannii.

scholarly journals Efficacy of Lysophosphatidylcholine as Direct Treatment in Combination with Colistin against Acinetobacter baumannii in Murine Severe Infections Models

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 194
Author(s):  
Andrea Miró-Canturri ◽  
Rafael Ayerbe-Algaba ◽  
Manuel Enrique Jiménez-Mejías ◽  
Jerónimo Pachón ◽  
Younes Smani
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Experimental Models ◽  
Antimicrobial Treatment ◽  
Clinical Settings ◽  
Monotherapy Group ◽  
Bacterial Concentration ◽  
Sepsis Model ◽  
Severe Infections ◽  
Stimulation Of

The stimulation of the immune response to prevent the progression of an infection may be an adjuvant to antimicrobial treatment. Here, we aimed to evaluate the efficacy of lysophosphatidylcholine (LPC) treatment in combination with colistin in murine experimental models of severe infections by Acinetobacter baumannii. We used the A. baumannii Ab9 strain, susceptible to colistin and most of the antibiotics used in clinical settings, and the A. baumannii Ab186 strain, susceptible to colistin but presenting a multidrug-resistant (MDR) pattern. The therapeutic efficacies of one and two LPC doses (25 mg/kg/d) and colistin (20 mg/kg/8 h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models. One and two LPC doses combined with colistin and colistin monotherapy enhanced Ab9 and Ab186 clearance from spleen, lungs and blood and reduced mice mortality compared with those of the non-treated mice group in both experimental models. Moreover, one and two LPC doses reduced the bacterial concentration in tissues and blood in both models and increased mice survival in the peritoneal sepsis model for both strains compared with those of the colistin monotherapy group. LPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the MDR A. baumannii infection.

scholarly journals Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Lipid A ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Resistance Mechanisms ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

scholarly journals Triclosan resistance in clinical isolates of Acinetobacter baumannii

2009 ◽  
Vol 58 (8) ◽  
pp. 1086-1091 ◽  
Author(s):  
Yagang Chen ◽  
Borui Pi ◽  
Hua Zhou ◽  
Yunsong Yu ◽  
Lanjuan Li
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Active Efflux ◽  
Low Level ◽  
High Level ◽  
Resistance Rates ◽  
Triclosan Resistance

The susceptibility to triclosan of 732 clinical Acinetobacter baumannii isolates obtained from 25 hospitals in 16 cities in China from December 2004 to December 2005 was screened by using an agar dilution method. Triclosan MICs ranged between 0.015 and 16 mg l−1, and the MIC90 was 0.5 mg l−1, lower than the actual in-use concentration of triclosan. Twenty triclosan-resistant isolates (MICs ≥1 mg l−1) were characterized by antibiotic susceptibility, clonal relatedness, fabI mutation, fabI expression, and efflux pump phenotype and expression to elucidate the resistance mechanism of A. baumannii to triclosan. The resistance rates of triclosan-resistant isolates to imipenem, levofloxacin, amikacin and tetracycline were higher than those of triclosan-sensitive isolates. Triclosan resistance was artificially classified as low level (MICs 1–2 mg l−1) or high level (MICs ≥4 mg l−1). High-level triclosan resistance could be explained by a Gly95Ser mutation of FabI, whilst wild-type fabI was observed to be overexpressed in low-level resistant isolates. Active efflux did not appear to be a major reason for acquired triclosan resistance, but acquisition of resistance appeared to be dependent on a background of intrinsic triclosan efflux.

scholarly journals Association of Efflux Pump and OMPs with Antibiotic Susceptibility Among ESBL-Producing Klebsiella Pneumoniae Clinical Strains in Malaysia

2021 ◽  
Author(s):  
Golnaz Mobasseri ◽  
Thong Kwai Lin ◽  
Cindy Shuan Ju Teh
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Antibiotic Susceptibility ◽  
Efflux Pump ◽  
Outer Membrane Proteins ◽  
Multidrug Resistant ◽  
Efflux Pump Inhibitor ◽  
Pump System ◽  
Extended Spectrum Beta Lactamases ◽  
Amoxicillin Clavulanate

Abstract Multidrug-resistant (MDR) Klebsiella pneumoniae (K. pneumoniae) poses a serious public health threat. K. pneumoniae strains that produce extended-spectrum beta-lactamases (ESBL) are becoming increasingly reported in nosocomial and community-acquired infections. Besides resistance genes, integrons, and plasmids, altered membrane permeability caused by porin loss and energy-dependent efflux have also contributed to antibiotic resistance in K. pneumoniae. The objective of this study was to determine the correlation between the reduction of antibiotic susceptibility and overexpression of efflux pump as well as the lack of outer membrane proteins (OMPs) among clinical ESBLs resistant K. pneumoniae. The expression levels of ramA, acrA, ompK35 and ompK36 in 12 MDR K. pneumoniae strains with varying MICs levels were analyzed using quantitative real time-Polymerase Chain Reaction (qRT-PCR). The role of efflux pump on antibiotic resistance was also studied by using minimum inhibitory concentration (MICs) method with//without efflux pump inhibitor. The result indicated that the strains with highest resistance to cefotaxime showed the lowest level of ompK35 and ompK36 genes expression while the strains with lowest MIC level of resistance to cefotaxime showed the highest level of expression of acrA and ramA. Our finding also revealed the effect of efflux pump inhibitor phenyl-arginine-b-naphthylamide (PAβN) on the MIC levels of ceftazidime, amoxicillin-clavulanate and cefotaxime which were significantly reduced around 1–7 folds MIC levels. These results suggest that Efflux pump system and deficiently of OMPs contributing role in antibiotic susceptibility which should be taken seriously to prevent the treatment failure due to antimicrobial resistance.

scholarly journals Multicity Outbreak of Carbapenem-Resistant Acinetobacter baumannii Isolates Producing the Carbapenemase OXA-40

2006 ◽  
Vol 50 (9) ◽  
pp. 2941-2945 ◽  
Author(s):  
Karen Lolans ◽  
Thomas W. Rice ◽  
L. Silvia Munoz-Price ◽  
John P. Quinn
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
The United States ◽  
Nucleotide Sequencing ◽  
Sequencing Analysis ◽  
Carbapenem Resistant ◽  
Extended Care ◽  
Care Facilities ◽  
High Level ◽  
First Time

ABSTRACT During 2005 we detected a multicity outbreak of infections or colonization due to high-level imipenem-resistant Acinetobacter baumannii (MIC, 64 μg/ml). One hundred isolates from diverse sources were obtained from seven acute-care hospitals and two extended-care facilities; 97% of the isolates belonged to one clone. Susceptibility testing of the first 42 isolates (January to April 2005) revealed broad resistance profiles. Half of the isolates were susceptible to ceftazidime, with many isolates susceptible only to colistin. The level of AmpC β-lactamase expression was stronger in isolates resistant to ceftazidime. PCR and subsequent nucleotide sequencing analysis identified bla OXA-40. The presence of an OXA-40 β-lactamase in these isolates correlated with the carbapenem resistance. By Southern blot analysis, a bla OXA-40-specific probe revealed that the gene was both plasmid and chromosomally located. This is the first time in the United States that such carbapenem resistance in A. baumannii has been attributable to a carbapenemase.

Efflux pump gene expression study using RNA-seq in multidrug-resistant TB

2021 ◽  
Vol 25 (12) ◽  
pp. 974-981
Author(s):  
J. J. Lee ◽  
H. Y. Kang ◽  
W-I. Lee ◽  
S. Y. Cho ◽  
Y. J. Kim ◽  
...  
Keyword(s):  
Wild Type Strain ◽  
Efflux Pump ◽  
Expression Patterns ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Regulatory Genes ◽  
Control Group ◽  
Rna Expression ◽  
Rna Seq ◽  
Expression Study

BACKGROUND: The mechanism underlying kanamycin (KM) resistance in Mycobacterium tuberculosis is not well understood, although efflux pump proteins are thought to play a role. This study used RNA-seq data to investigate changes in the expression levels of efflux pump genes following exposure to KM.METHODS: RNA expression of efflux pump and regulatory genes following exposure to different concentrations of KM (minimum inhibitory concentration MIC 25 and MIC50) in rrs wild-type strain and rrs A1401G mutated strain were compared with the control group.RESULTS: The selected strains had differential RNA expression patterns. Among the 71 putative efflux pump and regulatory genes, 46 had significant fold changes, and 12 genes (Rv0842, Rv1146, Rv1258c, Rv1473, Rv1686c, Rv1687c, Rv1877, Rv2038c, Rv3065, Rv3197a, Rv3728 and Rv3789) that were overexpressed following exposure to KM were thought to contribute to drug resistance. Rv3197A (whiB7) showed a distinct fold change based on the concentration of KM.CONCLUSION: The significant changes in the expression of the efflux pump and regulatory genes following exposure to KM may provide insights into the identification of a new resistance mechanism.

Sign in / Sign up

Export Citation Format

Share Document