A1 Refereed original research article in a scientific journal
Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration
Authors: Ruotsalainen P, Given C, Penttinen R, Jalasvuori M
Publisher: MDPI
Publication year: 2020
Journal: Antibiotics
Journal name in source: Antibiotics (Basel, Switzerland)
Journal acronym: Antibiotics (Basel)
Article number: 296
Volume: 9
Issue: 6
Number of pages: 9
ISSN: 2079-6382
eISSN: 2079-6382
DOI: https://doi.org/10.3390/antibiotics9060296
Web address : https://www.mdpi.com/2079-6382/9/6/296
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/47364796
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.
Downloadable publication This is an electronic reprint of the original article. |  |
