6.9.2019 Mobile “gene-scissors” target to prevent the spread of antibiotic resistance genes in bacterial communities (Ruotsalainen)

The decreased efficacy of antibiotics is a global problem and hinders the therapeutic outcome of previously treatable bacterial infections. In Europe, 33 000 people are estimated to die due to antibiotic resistant bacterial infections annually. Furthermore, these bacteria cause notable financial losts, for example in animal husbandry. In her doctoral dissertation at Ģֱ Pilvi Ruotsalainen developed mobile ”gene-scissors” which target and destroy antibiotic resistance genes and prevent their spread in bacterial communities.
Published
6.9.2019

Due to largely diminished pipeline for the development of new antibiotics, alternative treatments are urgently needed against antibiotic resistant bacterial infections. PhD candidate Pilvi Ruotsalainen developed mobile ”gene-scissors” (CRISPR-Cas9) which target specifically different antibiotic resistance genes.
These mobile ”gene-scissors” can spread from one bacterium to another in bacterial communities and destroy encountered antibiotic resistance genes by cutting the DNA. As a result, the bacterium’s  sensitivity to antibiotics is restored and it is unable to spread the resistance gene further to new bacteria.

Mobile ”gene-scissors” eliminate antibiotic resistance genes from bacteria

Besides developing new and potential treatment options, it is essential to understand how antibiotic resistance spreads in bacterial communities to prevent dispersal, says Pilvi Ruotsalainen. In her thesis, Ruotsalainen examined the spread of antibiotic resistance genes and the effect of different variables in their spread to sensitive bacteria.

Antibiotic resistance genes often reside in circular DNA molecules called plasmids, which can spread from one bacteria to another by conjugation. The results indicated that plasmids can rescue antibiotic sensitive bacteria even in lethal drug concentrations. Therefore, these sensitive bacteria can potentially acquire antibiotic resistance ”on the fly” even during otherwise effective antibiotic treatment.

”The spread of resistance plasmid into bacteria, targeted with antibiotics, would nullify the treatment outcome. Thus, it is essential to eliminate the antibiotic resistance genes for example from the symbiotic and harmless bacteria of gut microflora, as well. Perhaps in the future, we could use our mobile ”gene-scissors” for this”, Ruotsalainen contemplates.

Phages for treating bacterial infections

Bacterial viruses known as bacteriophages (or just phages) could also be used as a new treatment option to supplement antibiotics. Phages have been used to treat bacterial infections already at the beginning of 20th century also in the West. However, the discovery of antibiotics replaced phages as antimicrobials.

”The antibiotic crisis has raised new interest towards phages. They are natural enemies of bacteria and can effectively eliminate antibiotic resistant bacteria. Our results showed, that, if required, new phages can be readily isolated from environmental reservoirs for Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae”, Ruotsalainen says.

The dissertation is published JYU Dissertations series, number 107, ISSN 2489-9003, ISBN: 978-951-39-7819-8. Link to publication JYX archives:

M.Sc. Pilvi Ruotsalainen defends her doctoral dissertation in Cell and Molecular Biology "Extended-spectrum β-lactamase-producing Enterobacteriaceae: risks during antibiotic treatment and potential solutions to cure carriage" on Friday 6th of September at 12 o'clock at Ambiotica (YAA303) at Department of Biological and Environmental Science (Survontie 9, Ylistönrinne). Opponent is Professor Mikael Skurnik from University of Helsinki and Custos is Docent Matti Jalasvuori (Ģֱ). The doctoral dissertation is held in Finnish.

For further information
M.Sc Pilvi Ruotsalainen, pilvi.t.ruotsalainen@jyu.fi, tel.  +44 328 0903
Communications officer Tanja Heikkinen, tanja.s.heikkinen@jyu.fi, tel. +358 50 581 8351
The Faculty of Mathematics and Science 
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