Integrating Culture-based Antibiotic Resistance Profiles with Whole-genome Sequencing Data for 11,087 Clinical Isolates.
10.1016/j.gpb.2018.11.002
- Author:
Valentina GALATA
1
;
Cédric C LACZNY
1
;
Christina BACKES
1
;
Georg HEMMRICH-STANISAK
2
;
Susanne SCHMOLKE
3
;
Andre FRANKE
2
;
Eckart MEESE
4
;
Mathias HERRMANN
5
;
Lutz VON MÜLLER
5
;
Achim PLUM
6
,
7
;
Rolf MÜLLER
8
,
9
,
10
;
Cord STÄHLER
1
;
Andreas E POSCH
11
,
12
,
13
;
Andreas KELLER
14
Author Information
1. Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
2. Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany.
3. Siemens Healthcare GmbH, Strategy and Innovation, 91052 Erlangen, Germany.
4. Department of Human Genetics, Saarland University, 66421 Homburg, Germany.
5. Institute of Medical Microbiology and Hygiene, Saarland University, 66421 Homburg, Germany.
6. Ares Genetics GmbH, 1030 Vienna, Austria
7. Curetis GmbH, 71088 Holzgerlingen, Germany.
8. Department of Pharmacy, Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany
9. Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, 66123 Saarbrücken, Germany
10. Helmholtz Center for Infection Research and Pharmaceutical Biotechnology (HZI), Saarland University, 66123 Saarbrücken, Germany.
11. Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany
12. Ares Genetics GmbH, 1030 Vienna, Austria
13. Curetis GmbH, 71088 Holzgerlingen, Germany. Electronic address: andreas.posch@ares-genetics.com.
14. Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany. Electronic address: andreas.keller@uni-saarland.de.
- Publication Type:Journal Article
- Keywords:
Antibiotic resistance;
Bacteria;
Pan-genome;
Whole-genome sequencing
- MeSH:
Acinetobacter baumannii;
genetics;
isolation & purification;
Bacteria;
genetics;
isolation & purification;
Cell Culture Techniques;
methods;
Drug Resistance, Microbial;
genetics;
Escherichia coli;
genetics;
isolation & purification;
Genome, Bacterial;
Genotype;
Humans;
Internet;
Microbial Sensitivity Tests;
Phenotype;
Whole Genome Sequencing
- From:
Genomics, Proteomics & Bioinformatics
2019;17(2):169-182
- CountryChina
- Language:English
-
Abstract:
Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform molecular diagnostics and drug development. We collected genetic data (11,087 newly-sequenced whole genomes) and culture-based resistance profiles (10,991 out of the 11,087 isolates comprehensively tested against 22 antibiotics in total) of clinical isolates including 18 main species spanning a time period of 30 years. Species and drug specific resistance patterns were observed including increased resistance rates for Acinetobacter baumannii to carbapenems and for Escherichia coli to fluoroquinolones. Species-level pan-genomes were constructed to reflect the genetic repertoire of the respective species, including conserved essential genes and known resistance factors. Integrating phenotypes and genotypes through species-level pan-genomes allowed to infer gene-drug resistance associations using statistical testing. The isolate collection and the analysis results have been integrated into GEAR-base, a resource available for academic research use free of charge at https://gear-base.com.
