Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii
Antimicrobial resistance (AMR) in the nosocomial pathogen, Acinetobacter baumannii, is becoming a serious public health threat. While some mechanisms of AMR have been reported, understanding novel mechanisms of resistance is critical for identifying emerging resistance. One of the first steps in ide...
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doaj-433cd5746c42449ab6a16b0944a62bb92020-11-25T03:20:43ZengFrontiers Media S.A.Frontiers in Public Health2296-25652020-09-01810.3389/fpubh.2020.00451540704Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumanniiChandler Roe0Charles H. D. Williamson1Adam J. Vazquez2Kristen Kyger3Michael Valentine4Jolene R. Bowers5Paul D. Phillips6Veronica Harrison7Elizabeth Driebe8David M. Engelthaler9Jason W. Sahl10Northern Arizona University, Flagstaff, AZ, United StatesNorthern Arizona University, Flagstaff, AZ, United StatesNorthern Arizona University, Flagstaff, AZ, United StatesNorthern Arizona University, Flagstaff, AZ, United StatesTranslational Genomics Research Institute, Flagstaff, AZ, United StatesTranslational Genomics Research Institute, Flagstaff, AZ, United StatesNorthern Arizona University, Flagstaff, AZ, United StatesTranslational Genomics Research Institute, Flagstaff, AZ, United StatesTranslational Genomics Research Institute, Flagstaff, AZ, United StatesTranslational Genomics Research Institute, Flagstaff, AZ, United StatesNorthern Arizona University, Flagstaff, AZ, United StatesAntimicrobial resistance (AMR) in the nosocomial pathogen, Acinetobacter baumannii, is becoming a serious public health threat. While some mechanisms of AMR have been reported, understanding novel mechanisms of resistance is critical for identifying emerging resistance. One of the first steps in identifying novel AMR mechanisms is performing genotype/phenotype association studies; however, performing these studies is complicated by the plastic nature of the A. baumannii pan-genome. In this study, we compared the antibiograms of 12 antimicrobials associated with multiple drug families for 84 A. baumannii isolates, many isolated in Arizona, USA. in silico screening of these genomes for known AMR mechanisms failed to identify clear correlations for most drugs. We then performed a bacterial genome wide association study (bGWAS) looking for associations between all possible 21-mers; this approach generally failed to identify mechanisms that explained the resistance phenotype. In order to decrease the genomic noise associated with population stratification, we compared four phylogenetically-related pairs of isolates with differing susceptibility profiles. RNA-Sequencing (RNA-Seq) was performed on paired isolates and differentially-expressed genes were identified. In these isolate pairs, five different potential mechanisms were identified, highlighting the difficulty of broad AMR surveillance in this species. To verify and validate differential expression, amplicon sequencing was performed. These results suggest that a diagnostic platform based on gene expression rather than genomics alone may be beneficial in certain surveillance efforts. The implementation of such advanced diagnostics coupled with increased AMR surveillance will potentially improve A. baumannii infection treatment and patient outcomes.https://www.frontiersin.org/article/10.3389/fpubh.2020.00451/fullgenomicstranscriptomicsbioinformaticsacinetobacterAMR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chandler Roe Charles H. D. Williamson Adam J. Vazquez Kristen Kyger Michael Valentine Jolene R. Bowers Paul D. Phillips Veronica Harrison Elizabeth Driebe David M. Engelthaler Jason W. Sahl |
spellingShingle |
Chandler Roe Charles H. D. Williamson Adam J. Vazquez Kristen Kyger Michael Valentine Jolene R. Bowers Paul D. Phillips Veronica Harrison Elizabeth Driebe David M. Engelthaler Jason W. Sahl Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii Frontiers in Public Health genomics transcriptomics bioinformatics acinetobacter AMR |
author_facet |
Chandler Roe Charles H. D. Williamson Adam J. Vazquez Kristen Kyger Michael Valentine Jolene R. Bowers Paul D. Phillips Veronica Harrison Elizabeth Driebe David M. Engelthaler Jason W. Sahl |
author_sort |
Chandler Roe |
title |
Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii |
title_short |
Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii |
title_full |
Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii |
title_fullStr |
Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii |
title_full_unstemmed |
Bacterial Genome Wide Association Studies (bGWAS) and Transcriptomics Identifies Cryptic Antimicrobial Resistance Mechanisms in Acinetobacter baumannii |
title_sort |
bacterial genome wide association studies (bgwas) and transcriptomics identifies cryptic antimicrobial resistance mechanisms in acinetobacter baumannii |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Public Health |
issn |
2296-2565 |
publishDate |
2020-09-01 |
description |
Antimicrobial resistance (AMR) in the nosocomial pathogen, Acinetobacter baumannii, is becoming a serious public health threat. While some mechanisms of AMR have been reported, understanding novel mechanisms of resistance is critical for identifying emerging resistance. One of the first steps in identifying novel AMR mechanisms is performing genotype/phenotype association studies; however, performing these studies is complicated by the plastic nature of the A. baumannii pan-genome. In this study, we compared the antibiograms of 12 antimicrobials associated with multiple drug families for 84 A. baumannii isolates, many isolated in Arizona, USA. in silico screening of these genomes for known AMR mechanisms failed to identify clear correlations for most drugs. We then performed a bacterial genome wide association study (bGWAS) looking for associations between all possible 21-mers; this approach generally failed to identify mechanisms that explained the resistance phenotype. In order to decrease the genomic noise associated with population stratification, we compared four phylogenetically-related pairs of isolates with differing susceptibility profiles. RNA-Sequencing (RNA-Seq) was performed on paired isolates and differentially-expressed genes were identified. In these isolate pairs, five different potential mechanisms were identified, highlighting the difficulty of broad AMR surveillance in this species. To verify and validate differential expression, amplicon sequencing was performed. These results suggest that a diagnostic platform based on gene expression rather than genomics alone may be beneficial in certain surveillance efforts. The implementation of such advanced diagnostics coupled with increased AMR surveillance will potentially improve A. baumannii infection treatment and patient outcomes. |
topic |
genomics transcriptomics bioinformatics acinetobacter AMR |
url |
https://www.frontiersin.org/article/10.3389/fpubh.2020.00451/full |
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