Cargando…

Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration

Beta-lactams are commonly used antibiotics that prevent cell-wall biosynthesis. Beta-lactam sensitive bacteria can acquire conjugative resistance elements and hence become resistant even after being exposed to lethal (above minimum inhibitory) antibiotic concentrations. Here we show that neither the...

Descripción completa

Detalles Bibliográficos
Autores principales: Ruotsalainen, Pilvi, Given, Cindy, Penttinen, Reetta, Jalasvuori, Matti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345503/
https://www.ncbi.nlm.nih.gov/pubmed/32498393
http://dx.doi.org/10.3390/antibiotics9060296
_version_ 1783556198317948928
author Ruotsalainen, Pilvi
Given, Cindy
Penttinen, Reetta
Jalasvuori, Matti
author_facet Ruotsalainen, Pilvi
Given, Cindy
Penttinen, Reetta
Jalasvuori, Matti
author_sort Ruotsalainen, Pilvi
collection PubMed
description Beta-lactams are commonly used antibiotics that prevent cell-wall biosynthesis. Beta-lactam sensitive bacteria can acquire conjugative resistance elements and hence become resistant even after being exposed to lethal (above minimum inhibitory) antibiotic concentrations. Here we show that neither the length of antibiotic exposure (1 to 16 h) nor the beta-lactam type (penam or cephem) have a major impact on the rescue of sensitive bacteria. We demonstrate that an evolutionary rescue can occur between different clinically relevant bacterial species (Klebsiella pneumoniae and Escherichia coli) by plasmids that are commonly associated with extended-spectrum beta-lactamase (ESBL) positive hospital isolates. As such, it is possible that this resistance dynamic may play a role in failing antibiotic therapies in those cases where resistant bacteria may readily migrate into the proximity of sensitive pathogens. Furthermore, we engineered a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-plasmid to encode a guiding CRISPR-RNA against the migrating ESBL-plasmid. By introducing this plasmid into the sensitive bacterium, the frequency of the evolutionarily rescued bacteria decreased by several orders of magnitude. As such, engineering pathogens during antibiotic treatment may provide ways to prevent ESBL-plasmid dispersal and hence resistance evolution.
format Online
Article
Text
id pubmed-7345503
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-73455032020-07-09 Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration Ruotsalainen, Pilvi Given, Cindy Penttinen, Reetta Jalasvuori, Matti Antibiotics (Basel) Article Beta-lactams are commonly used antibiotics that prevent cell-wall biosynthesis. Beta-lactam sensitive bacteria can acquire conjugative resistance elements and hence become resistant even after being exposed to lethal (above minimum inhibitory) antibiotic concentrations. Here we show that neither the length of antibiotic exposure (1 to 16 h) nor the beta-lactam type (penam or cephem) have a major impact on the rescue of sensitive bacteria. We demonstrate that an evolutionary rescue can occur between different clinically relevant bacterial species (Klebsiella pneumoniae and Escherichia coli) by plasmids that are commonly associated with extended-spectrum beta-lactamase (ESBL) positive hospital isolates. As such, it is possible that this resistance dynamic may play a role in failing antibiotic therapies in those cases where resistant bacteria may readily migrate into the proximity of sensitive pathogens. Furthermore, we engineered a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-plasmid to encode a guiding CRISPR-RNA against the migrating ESBL-plasmid. By introducing this plasmid into the sensitive bacterium, the frequency of the evolutionarily rescued bacteria decreased by several orders of magnitude. As such, engineering pathogens during antibiotic treatment may provide ways to prevent ESBL-plasmid dispersal and hence resistance evolution. MDPI 2020-06-02 /pmc/articles/PMC7345503/ /pubmed/32498393 http://dx.doi.org/10.3390/antibiotics9060296 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ruotsalainen, Pilvi
Given, Cindy
Penttinen, Reetta
Jalasvuori, Matti
Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration
title Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration
title_full Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration
title_fullStr Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration
title_full_unstemmed Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration
title_short Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration
title_sort beta-lactam sensitive bacteria can acquire esbl-resistance via conjugation after long-term exposure to lethal antibiotic concentration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345503/
https://www.ncbi.nlm.nih.gov/pubmed/32498393
http://dx.doi.org/10.3390/antibiotics9060296
work_keys_str_mv AT ruotsalainenpilvi betalactamsensitivebacteriacanacquireesblresistanceviaconjugationafterlongtermexposuretolethalantibioticconcentration
AT givencindy betalactamsensitivebacteriacanacquireesblresistanceviaconjugationafterlongtermexposuretolethalantibioticconcentration
AT penttinenreetta betalactamsensitivebacteriacanacquireesblresistanceviaconjugationafterlongtermexposuretolethalantibioticconcentration
AT jalasvuorimatti betalactamsensitivebacteriacanacquireesblresistanceviaconjugationafterlongtermexposuretolethalantibioticconcentration