A1 Journal article (refereed)
Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration (2020)

Ruotsalainen, P., Given, C., Penttinen, R., & Jalasvuori, M. (2020). Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration. Antibiotics, 9(6), Article 296. https://doi.org/10.3390/antibiotics9060296

JYU authors or editors

Publication details

All authors or editors: Ruotsalainen, Pilvi; Given, Cindy; Penttinen, Reetta; Jalasvuori, Matti

Journal or series: Antibiotics

eISSN: 2079-6382

Publication year: 2020

Volume: 9

Issue number: 6

Article number: 296

Publisher: MDPI

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/antibiotics9060296

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/69784


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.

Keywords: bacteria; Klebsiella; Escherichia coli; antibiotic resistance; antibiotics; horizontal gene transfer; plasmids

Free keywords: antibiotic resistance; extended-spectrum beta-lactamase; evolutionary rescue; conjugative plasmid

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Ministry reporting: Yes

Reporting Year: 2020

JUFO rating: 1

Last updated on 2021-07-07 at 21:34