Dataset Information

Revisiting Polymorphic Diversity of Aminoglycoside N-Acetyltransferase AAC(6')-Ib Based on Bacterial Genomes of Human, Animal, and Environmental Origins.

ABSTRACT: The prevalence of aac(6')-Ib variants has been demonstrated in numerous epidemiological studies. We revisited the polymorphic diversity of aminoglycoside 6'-N-acetyltransferase gene [aac(6')-Ib] in the bacterial genome databases based on One Health perspectives. aac(6')-Ib was searched against bacterial complete and draft genome databases of NCBI. Based on the major polymorphic residues 102, 117, and 179, taxonomy, ecology, and temporal emergence of bacterial isolates harboring variants of aac(6')-Ib gene were evaluated using whole-genome sequences available in the databases. A total of 3,964 aac(6')-Ib sequences were found to be present in the genomes of 34 bacterial genera, mostly found in Gammaproteobacteria. Among these, aac(6')-Ib-cr variant, known to confer fluoroquinolone resistance, were increasingly detected in bacterial genomes and most abundant in the genera Klebsiella and Escherichia, thereby suggesting that these genera were the major reservoirs of the plasmid-mediated quinolone resistance (PMQR) determinant. The proportions of the cr variant were higher in animal and environmental isolates than in human isolates, among which the variant was dominant (>50%) in the genomes of intestinal, rectal, and fecal origins. In addition, our study suggested that the prevalence of the cr variant was associated with the occurrence of a variant with the mutation L117 (IbL). An integrated surveillance system for antimicrobial resistance in human, animal, and environmental sectors, based on whole-genome sequencing, would provide a better insight into the evolution, ecology, and epidemiology of antimicrobial-resistant bacteria.

SUBMITTER: Kim DW

PROVIDER: S-EPMC6095969 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Revisiting Polymorphic Diversity of Aminoglycoside N-Acetyltransferase AAC(6')-Ib Based on Bacterial Genomes of Human, Animal, and Environmental Origins.

Kim Dae-Wi DW Thawng Cung N CN Lee Kihyun K Cha Chang-Jun CJ

Frontiers in microbiology 20180810

The prevalence of aac(6')-Ib variants has been demonstrated in numerous epidemiological studies. We revisited the polymorphic diversity of aminoglycoside 6'-N-acetyltransferase gene [aac(6')-Ib] in the bacterial genome databases based on One Health perspectives. aac(6')-Ib was searched against bacterial complete and draft genome databases of NCBI. Based on the major polymorphic residues 102, 117, and 179, taxonomy, ecology, and temporal emergence of bacterial isolates ...[more]

PMID: 30147681

Similar Datasets

Project description:The aminoglycoside 6'-N-acetyltransferase type Ib (AAC(6')-Ib) is a common cause of resistance to amikacin and other aminoglycosides in Gram-negatives. Utilization of mixture-based combinatorial libraries and application of the positional scanning strategy identified an inhibitor of AAC(6')-Ib. This inhibitor's chemical structure consists of a pyrrolidine pentamine scaffold substituted at four locations (R1, R3, R4, and R5). The substituents are two S-phenyl groups (R1 and R4), an S-hydroxymethyl group (R3), and a 3-phenylbutyl group (R5). Another location, R2, does not have a substitution, but it is named because its stereochemistry was modified in some compounds utilized in this study. Structure-activity relationship (SAR) analysis using derivatives with different functionalities, modified stereochemistry, and truncations was carried out by assessing the effect of the addition of each compound at 8 µM to 16 µg/mL amikacin-containing media and performing checkerboard assays varying the concentrations of the inhibitor analogs and the antibiotic. The results show that: (1) the aromatic functionalities at R1 and R4 are essential, but the stereochemistry is essential only at R4; (2) the stereochemical conformation at R2 is critical; (3) the hydroxyl moiety at R3 as well as stereoconformation are required for full inhibitory activity; (4) the phenyl functionality at R5 is not essential and can be replaced by aliphatic groups; (5) the location of the phenyl group on the butyl carbon chain at R5 is not essential; (6) the length of the aliphatic chain at R5 is not critical; and (7) all truncations of the scaffold resulted in inactive compounds. Molecular docking revealed that all compounds preferentially bind to the kanamycin C binding cavity, and binding affinity correlates with the experimental data for most of the compounds evaluated. The SAR results in this study will serve as the basis for the design of new analogs in an effort to improve their ability to induce phenotypic conversion to susceptibility in amikacin-resistant pathogens.

Dataset Information

Revisiting Polymorphic Diversity of Aminoglycoside N-Acetyltransferase AAC(6')-Ib Based on Bacterial Genomes of Human, Animal, and Environmental Origins.

Publications

Revisiting Polymorphic Diversity of Aminoglycoside <i>N</i>-Acetyltransferase AAC(6')-Ib Based on Bacterial Genomes of Human, Animal, and Environmental Origins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets