Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genomewide analysis of divergence of antibiotic resistance determinants in closely related isolates of Acinetobacter baumannii.

ABSTRACT: Multidrug resistance has emerged as a significant concern with infections caused by Acinetobacter baumannii. Ample evidence supports the involvement of mobile genetic elements in the transfer of antibiotic resistance genes, but the extent of variability and the rate of genetic change associated with the acquisition of antibiotic resistance have not been studied in detail. Whole-genome sequence analysis of six closely related clinical isolates of A. baumannii, including four from the same hospital, revealed extensive divergence of the resistance genotype that correlated with observed differences in antimicrobial susceptibility. Resistance genes associated with insertion sequences, plasmids, and a chromosomal resistance gene island all showed variability. The highly dynamic resistance gene repertoire suggests rapid evolution of drug resistance.

SUBMITTER: Adams MD

PROVIDER: S-EPMC2934971 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Genomewide analysis of divergence of antibiotic resistance determinants in closely related isolates of Acinetobacter baumannii.

Adams Mark D MD Chan E Ricky ER Molyneaux Neil D ND Bonomo Robert A RA

Antimicrobial agents and chemotherapy 20100607 9

Multidrug resistance has emerged as a significant concern with infections caused by Acinetobacter baumannii. Ample evidence supports the involvement of mobile genetic elements in the transfer of antibiotic resistance genes, but the extent of variability and the rate of genetic change associated with the acquisition of antibiotic resistance have not been studied in detail. Whole-genome sequence analysis of six closely related clinical isolates of A. baumannii, including four from the same hospita ...[more]

PMID: 20530228

Similar Datasets

DNA microarray for genotyping antibiotic resistance determinants in Acinetobacter baumannii clinical isolates.

Project description:In recent decades, Acinetobacter baumannii has emerged as an organism of great concern due to its ability to accumulate antibiotic resistance. In order to improve the diagnosis of resistance determinants in A. baumannii in terms of lead time and accuracy, we developed a microarray that can be used to detect 91 target sequences associated with antibiotic resistance within 4 h from bacterial culture to result. The array was validated with 60 multidrug-resistant strains of A. baumannii in a blinded, prospective study. The results were compared to phenotype results determined by the automated susceptibility testing system VITEK2. Antibiotics considered were piperacillin-tazobactam, ceftazidime, imipenem, meropenem, trimethoprim-sulfamethoxazole, amikacin, gentamicin, tobramycin, ciprofloxacin, and tigecycline. The average positive predictive value, negative predictive value, sensitivity, and specificity were 98, 98, 99, and 94%, respectively. For carbapenemase genes, the array results were compared to singleplex PCR results provided by the German National Reference Center for Gram-Negative Pathogens, and results were in complete concordance. The presented array is able to detect all relevant resistance determinants of A. baumannii in parallel. The short handling time of 4 h from culture to result helps to provide fast results in order to initiate adequate anti-infective therapy for critically ill patients. Another application would be data acquisition for epidemiologic surveillance.

| S-EPMC3811405 | biostudies-literature

Mobile Genetic Elements Harboring Antibiotic Resistance Determinants in Acinetobacter baumannii Isolates From Bolivia.

Project description:Using a combination of short- and long-read DNA sequencing, we have investigated the location of antibiotic resistance genes and characterized mobile genetic elements (MGEs) in three clinical multi-drug resistant Acinetobacter baumannii. The isolates, collected in Bolivia, clustered separately with three different international clonal lineages. We found a diverse array of transposons, plasmids and resistance islands related to different insertion sequence (IS) elements, which were located in both the chromosome and in plasmids, which conferred resistance to multiple antimicrobials, including carbapenems. Carbapenem resistance might be caused by a Tn2008 carrying the bla OXA-23 gene. Some plasmids were shared between the isolates. Larger plasmids were less conserved than smaller ones and they shared some homologous regions, while others were more diverse, suggesting that these big plasmids are more plastic than the smaller ones. The genetic basis of antimicrobial resistance in Bolivia has not been deeply studied until now, and the mobilome of these A. baumannii isolates, combined with their multi-drug resistant phenotype, mirror the transfer and prevalence of MGEs contributing to the spread of antibiotic resistance worldwide and require special attention. These findings could be useful to understand the antimicrobial resistance genetics of A. baumannii in Bolivia and the difficulty in tackling these infections.

| S-EPMC7237729 | biostudies-literature

Comparative genomic analysis of Acinetobacter baumannii clinical isolates reveals extensive genomic variation and diverse antibiotic resistance determinants.

Project description:BACKGROUND: Acinetobacter baumannii is an important nosocomial pathogen that poses a serious health threat to immune-compromised patients. Due to its rapid ability to develop multidrug resistance (MDR), A. baumannii has increasingly become a focus of attention worldwide. To better understand the genetic variation and antibiotic resistance mechanisms of this bacterium at the genomic level, we reported high-quality draft genome sequences of 8 clinical isolates with various sequence types and drug susceptibility profiles. RESULTS: We sequenced 7 MDR and 1 drug-sensitive clinical A. baumannii isolates and performed comparative genomic analysis of these draft genomes with 16 A. baumannii complete genomes from GenBank. We found a high degree of variation in A. baumannii, including single nucleotide polymorphisms (SNPs) and large DNA fragment variations in the AbaR-like resistance island (RI) regions, the prophage and the type VI secretion system (T6SS). In addition, we found several new AbaR-like RI regions with highly variable structures in our MDR strains. Interestingly, we found a novel genomic island (designated as GIBJ4) in the drug-sensitive strain BJ4 carrying metal resistance genes instead of antibiotic resistance genes inserted into the position where AbaR-like RIs commonly reside in other A. baumannii strains. Furthermore, we showed that diverse antibiotic resistance determinants are present outside the RIs in A. baumannii, including antibiotic resistance-gene bearing integrons, the blaOXA-23-containing transposon Tn2009, and chromosomal intrinsic antibiotic resistance genes. CONCLUSIONS: Our comparative genomic analysis revealed that extensive genomic variation exists in the A. baumannii genome. Transposons, genomic islands and point mutations are the main contributors to the plasticity of the A. baumannii genome and play critical roles in facilitating the development of antibiotic resistance in the clinical isolates.

| S-EPMC4367897 | biostudies-literature

Biofilm-Induced Antibiotic Resistance in Clinical <i>Acinetobacter baumannii</i> Isolates.

Project description:In order to understand the role of biofilm in the emergence of antibiotic resistance, a total of 104 clinical Acinetobacter baumannii strains were investigated for their biofilm-forming capacities and genes associated with biofilm formation. Selected biofilm-formers were tested for antibiotic susceptibilities when grown in biofilm phase. Reversibility of antibiotic susceptibility in planktonic cells regrown from biofilm were investigated. We found 59.6% of the strains were biofilm-formers, among which, 66.1% were non-multidrug resistant (MDR) strains. Presence of virulence genes bap, csuE, and abaI was significantly associated with biofilm-forming capacities. When strains were grown in biofilm state, the minimum biofilm eradication concentrations were 44, 407, and 364 times higher than the minimum bactericidal concentrations (MBC) for colistin, ciprofloxacin, and imipenem, respectively. Persisters were detected after treating the biofilm at 32-256 times the MBC of planktonic cells. Reversibility test for antibiotic susceptibility showed that biofilm formation induced reversible antibiotic tolerance in the non-MDR strains but a higher level of irreversible resistance in the extensively drug-resistant (XDR) strain. In summary, we showed that the non-MDR strains were strong biofilm-formers. Presence of persisters in biofilm contributed to the reduced antibiotic susceptibilities. Biofilm-grown Acinetobacter baumannii has induced antibiotic tolerance in non-MDR strains and increased resistance levels in XDR strains. To address the regulatory mechanisms of biofilm-specific resistance, thorough investigations at genome and transcription levels are warranted.

| S-EPMC7698371 | biostudies-literature

AbGRI4, a novel antibiotic resistance island in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates.

Project description:ObjectivesTo investigate the genomic context of a novel resistance island (RI) in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates and global isolates.MethodsUsing a combination of long and short reads generated from the Oxford Nanopore and Illumina platforms, contiguous chromosomes and plasmid sequences were determined. BLAST-based analysis was used to identify the RI insertion target.ResultsGenomes of four multiply antibiotic-resistant A. baumannii clinical strains, from a US hospital system, belonging to prevalent MLST ST2 (Pasteur scheme) and ST281 (Oxford scheme) clade F isolates were sequenced to completion. A class 1 integron carrying aadB (tobramycin resistance) and aadA2 (streptomycin/spectinomycin resistance) was identified. The class 1 integron was 6.8 kb, bounded by IS26 at both ends, and embedded in a new target location between an α/β-hydrolase and a reductase. Due to its novel insertion site and unique RI composition, we suggest naming this novel RI AbGRI4. Molecular analysis of global A. baumannii isolates identified multiple AbGRI4 RI variants in non-ST2 clonal lineages, including variations in the resistance gene cassettes, integron backbone and insertion breakpoints at the hydrolase gene.ConclusionsA novel RI insertion target harbouring a class 1 integron was identified in a subgroup of ST2/ST281 clinical isolates. Variants of the RI suggested evolution and horizontal transfer of the RI across clonal lineages. Long- and short-read hybrid assembly technology completely resolved the genomic context of IS-bounded RIs, which was not possible using short reads alone.

| S-EPMC7556812 | biostudies-literature

Antimicrobial resistance determinants in Acinetobacter baumannii isolates taken from military treatment facilities.

Project description:Multidrug-resistant (MDR) Acinetobacter baumannii infections are of particular concern within medical treatment facilities, yet the gene assemblages that give rise to this phenotype remain poorly characterized. In this study, we tested 97 clinical A. baumannii isolates collected from military treatment facilities (MTFs) from 2003 to 2009 by using a molecular epidemiological approach that enabled for the simultaneous screening of 236 antimicrobial resistance genes. Overall, 80% of the isolates were found to be MDR, each strain harbored between one and 17 resistant determinants, and a total of 52 unique resistance determinants or gene families were detected which are known to confer resistance to ?-lactam (e.g., blaGES-11, blaTEM, blaOXA-58), aminoglycoside (e.g., aphA1, aacC1, armA), macrolide (msrA, msrB), tetracycline [e.g., tet(A), tet(B), tet(39)], phenicol (e.g., cmlA4, catA1, cat4), quaternary amine (qacE, qacE?1), streptothricin (sat2), sulfonamide (sul1, sul2), and diaminopyrimidine (dfrA1, dfrA7, dfrA19) antimicrobial compounds. Importantly, 91% of the isolates harbored blaOXA-51-like carbapenemase genes (including six new variants), 40% harbored the blaOXA-23 carbapenemase gene, and 89% contained a variety of aminoglycoside resistance determinants with up to six unique determinants identified per strain. Many of the resistance determinants were found in potentially mobile gene cassettes; 45% and 7% of the isolates contained class 1 and class 2 integrons, respectively. Combined, the results demonstrate a facile approach that supports a more complete understanding of the genetic underpinnings of antimicrobial resistance to better assess the load, transmission, and evolution of MDR in MTF-associated A. baumannii.

| S-EPMC3910874 | biostudies-literature

Antimicrobial Resistance Determinants in Genomes and Plasmids from Acinetobacter baumannii Clinical Isolates.

Project description:Acinetobacter baumannii is a Gram-negative coccoid rod species, clinically relevant as a human pathogen, included in the ESKAPE group. Carbapenem-resistant A. baumannii (CRAB) are considered by the World Health Organization (WHO) as a critical priority pathogen for the research and development of new antibiotics. Some of the most relevant features of this pathogen are its intrinsic multidrug resistance and its ability to acquire rapid and effective new resistant determinants against last-resort clinical antibiotics, mostly from other ESKAPE species. The presence of plasmids and mobile genetic elements in their genomes contributes to the acquisition of new antimicrobial resistance determinants. However, although A. baumannii has arisen as an important human pathogen, information about these elements is still not well understood. Current genomic analysis availability has increased our ability to understand the microevolution of bacterial pathogens, including point mutations, genetic dissemination, genomic stability, and pan- and core-genome compositions. In this work, we deeply studied the genomes of four clinical strains from our hospital, and the reference strain ATCC®19606TM, which have shown a remarkable ability to survive and maintain their effective capacity when subjected to long-term stress conditions. With that, our aim was presenting a detailed analysis of their genomes, including antibiotic resistance determinants and plasmid composition.

| S-EPMC8300758 | biostudies-literature

Acinetobacter baumannii Efflux Pumps and Antibiotic Resistance.

Project description:Acinetobacter baumannii is a nosocomial pathogen and gram-negative coccobacillus that is responsible for opportunistic infections, pneumonia, and infections of the urinary tract, bloodstream, skin, and soft tissue. This bacterium poses a major public health problem due to inducing resistance to several drugs, isolates, multidrug treatment, and occasionally pan drugs. Drug resistance is not only a major concern caused by A. baumannii but also is considered as the main challenge in many other pathogens. Several factors such as the efflux pump are associated with antibiotic resistance, biofilm production, and genetic mutations. In this review, A. baumannii is introduced in then some of the practical works conducted on the existing efflux pump are reviewed. The importance of the efflux pump is considered in this paper in relation to the antibiotic resistance and mechanisms developed for the inhibition of these pumps as well.

| S-EPMC7024869 | biostudies-literature

Acinetobacter baumannii biofilms: effects of physicochemical factors, virulence, antibiotic resistance determinants, gene regulation, and future antimicrobial treatments.

Project description:Acinetobacter baumannii is a leading cause of nosocomial infections due to its increased antibiotic resistance and virulence. The ability of A. baumannii to form biofilms contributes to its survival in adverse environmental conditions including hospital environments and medical devices. A. baumannii has undoubtedly propelled the interest of biomedical researchers due to its broad range of associated infections especially in hospital intensive care units. The interplay among microbial physicochemistry, alterations in the phenotype and genotypic determinants, and the impact of existing ecological niche and the chemistry of antimicrobial agents has led to enhanced biofilm formation resulting in limited access of drugs to their specific targets. Understanding the triggers to biofilm formation is a step towards limiting and containing biofilm-associated infections and development of biofilm-specific countermeasures. The present review therefore focused on explaining the impact of environmental factors, antimicrobial resistance, gene alteration and regulation, and the prevailing microbial ecology in A. baumannii biofilm formation and gives insights into prospective anti-infective treatments.

| S-EPMC6245380 | biostudies-literature

Role of plasmid carrying bla NDM in mediating antibiotic resistance among Acinetobacter baumannii clinical isolates from Egypt.

Project description:We investigated antibiotic resistance levels among bla NDM -positive (n = 9) and -negative (n = 65) A. baumannii clinical isolates collected in 2010 and 2015 from Alexandria Main University Hospital, Egypt using disc diffusion and minimum inhibitory concentration (MIC) determination. Plasmids from bla NDM -positive isolates were transformed into a carbapenem-susceptible A. baumannii (CS-AB) isolate to assess the role of plasmid transfer in mediating carbapenem resistance. Imipenem, meropenem, and ertapenem MIC90 values against bla NDM -positive isolates were 128, > 256, and 256 µg/mL, respectively. Plasmid isolation and polymerase chain reaction revealed that bla NDM was plasmid mediated. The plasmids were electroporated into the cells of a CS-AB isolate at an efficiency of 1.3 × 10-8 to 2.6 × 10-7, transforming them to bla NDM -positive carbapenem-resistant cells with an imipenem MIC increase of 256-fold. In addition to carbapenem resistance, the bla NDM -positive isolates also exhibited higher levels of cephalosporins, tetracycline, aminoglycosides, fluoroquinolones, and colistin resistance than the bla NDM -negative isolates. Acquisition of bla NDM -carrying plasmids dramatically increased imipenem resistance among A. baumannii isolates. Intriguingly, bla NDM -positive isolates also showed a high degree of resistance to antibiotics of different classes. The potential co-existence of different resistance determinants on A. baumannii plasmids and their possible transfer owing to the natural competence of the pathogen are especially alarming. More effective infection control and antibiotic stewardship programs are needed to curb the spread and treat such infections in both hospital and community settings.

| S-EPMC7076099 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data