---
_id: '10271'
abstract:
- lang: eng
text: Understanding interactions between antibiotics used in combination is an important
theme in microbiology. Using the interactions between the antifolate drug trimethoprim
and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model,
we applied a transcriptomic approach for dissecting interactions between two antibiotics
with different modes of action. When trimethoprim and erythromycin were combined,
the transcriptional response of genes from the sulfate reduction pathway deviated
from the dominant effect of trimethoprim on the transcriptome. We successfully
altered the drug interaction from additivity to suppression by increasing the
sulfate level in the growth environment and identified sulfate reduction as an
important metabolic determinant that shapes the interaction between the two drugs.
Our work highlights the potential of using prioritization of gene expression patterns
as a tool for identifying key metabolic determinants that shape drug-drug interactions.
We further demonstrated that the sigma factor-binding protein gene crl shapes
the interactions between the two antibiotics, which provides a rare example of
how naturally occurring variations between strains of the same bacterial species
can sometimes generate very different drug interactions.
acknowledgement: High-throughput sequencing data were generated by the Vienna BioCenter
Core Facilities. The authors would like to thank Karin Mitosch, Bor Kavcic, and
Nadine Kraupner for their constructive feedback. The authors would also like to
thank Gertraud Stift, Julia Flor, Renate Srsek, Agnieszka Wiktor, and Booshini Fernando
for technical support.
article_number: '760017'
article_processing_charge: No
article_type: original
author:
- first_name: Qin
full_name: Qi, Qin
id: 3B22D412-F248-11E8-B48F-1D18A9856A87
last_name: Qi
orcid: 0000-0002-6148-2416
- first_name: S. Andreas
full_name: Angermayr, S. Andreas
last_name: Angermayr
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Qi Q, Angermayr SA, Bollenbach MT. Uncovering Key Metabolic Determinants of
the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli.
Frontiers in Microbiology. 2021;12. doi:10.3389/fmicb.2021.760017
apa: Qi, Q., Angermayr, S. A., & Bollenbach, M. T. (2021). Uncovering Key Metabolic
Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in
Escherichia coli. Frontiers in Microbiology. Frontiers. https://doi.org/10.3389/fmicb.2021.760017
chicago: Qi, Qin, S. Andreas Angermayr, and Mark Tobias Bollenbach. “Uncovering
Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin
in Escherichia Coli.” Frontiers in Microbiology. Frontiers, 2021. https://doi.org/10.3389/fmicb.2021.760017.
ieee: Q. Qi, S. A. Angermayr, and M. T. Bollenbach, “Uncovering Key Metabolic Determinants
of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia
coli,” Frontiers in Microbiology, vol. 12. Frontiers, 2021.
ista: Qi Q, Angermayr SA, Bollenbach MT. 2021. Uncovering Key Metabolic Determinants
of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia
coli. Frontiers in Microbiology. 12, 760017.
mla: Qi, Qin, et al. “Uncovering Key Metabolic Determinants of the Drug Interactions
Between Trimethoprim and Erythromycin in Escherichia Coli.” Frontiers in Microbiology,
vol. 12, 760017, Frontiers, 2021, doi:10.3389/fmicb.2021.760017.
short: Q. Qi, S.A. Angermayr, M.T. Bollenbach, Frontiers in Microbiology 12 (2021).
date_created: 2021-11-11T10:39:37Z
date_published: 2021-10-20T00:00:00Z
date_updated: 2023-08-14T11:43:23Z
day: '20'
ddc:
- '610'
doi: 10.3389/fmicb.2021.760017
ec_funded: 1
external_id:
isi:
- '000715997300001'
pmid:
- '34745067'
file:
- access_level: open_access
checksum: d41321748e9588dd3cf03e9a7222127f
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-11T10:54:40Z
date_updated: 2021-11-11T10:54:40Z
file_id: '10272'
file_name: 2021_FrontiersMicrob_Qi.pdf
file_size: 2397203
relation: main_file
success: 1
file_date_updated: 2021-11-11T10:54:40Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
keyword:
- microbiology
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 25E83C2C-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303507'
name: Optimality principles in responses to antibiotics
publication: Frontiers in Microbiology
publication_identifier:
eissn:
- 1664-302X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim
and Erythromycin in Escherichia coli
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...