Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antibiotic exposure can 'prime' single-resistant bacteria to become multidrug-resistant

28.04.2020

Antibiotics save lives -- but using them also helps antibiotic-resistant strains evolve and spread. Each year, antibiotic-resistant bacteria infect some 2.8 million people in the United States, killing more than 35,000, according to the Centers for Disease Control and Prevention. Infections by multidrug-resistant -- or MDR -- bacteria, which are resistant to two or more antibiotics, are particularly difficult to treat.

Scientists at the University of Washington and the University of Idaho have discovered just how readily MDR bacteria can emerge. In a paper published April 6 in Nature Ecology & Evolution, the researchers report that, for a bacterial pathogen already resistant to an antibiotic, prolonged exposure to that antibiotic not only boosted its ability to retain its resistance gene, but also made the pathogen more readily pick up and maintain resistance to a second antibiotic and become a MDR strain.


This is a colorized scanning electron micrograph image of Klebsiella pneumoniae interacting with a human neutrophil, a type of white blood cell.

Credit: National Institute of Allergy and Infectious Diseases

The team's experiments indicate that prolonged exposure to one type of antibiotic essentially "primed" the bacteria. This priming effect made it more likely that the bacteria would acquire resistance to additional antibiotics, even in the absence of further antibiotic exposure, and helped the strain hold on to those antibiotic-resistance traits for generations.

"Exposure to antibiotics appears to select indirectly for more stable antibiotic resistance systems," said Benjamin Kerr, a UW professor of biology and co-senior author on the paper. "A more stable system in a strain will increase the chances that it will acquire resistance to multiple antibiotics."

Their findings also show how antibiotic exposure affects the evolutionary dynamics within bacteria.

"This could help explain not only the rise of multidrug resistance in bacteria, but also how antibiotic resistance persists and spreads in the environment -- in health care settings, in soil from agricultural runoff -- even long after the antibiotic exposure has ended," said co-senior author Eva Top, a professor of biology at the University of Idaho.

The researchers tested a common mechanism for the spread of antibiotic resistance: plasmids. These are circular strands of DNA that can contain many types of genes, including genes for antibiotic resistance. Bacteria easily share plasmids, even across species.

Yet plasmids have their downsides, and past research has shown that bacteria readily shed them.

"Even though they can carry beneficial genes, plasmids can also interfere with many types of processes inside a bacterial cell, such as metabolism or DNA replication," said lead author Hannah Jordt, a UW research scientist in biology. "So, scientists have generally thought of plasmids as costly and burdensome to the host cell."

The UW-University of Idaho team worked with E. coli cells containing a tetracycline-resistance plasmid and Klebsiella pneumoniae cells containing a chloramphenicol-resistance plasmid. Both hosts, which had not been grown in the presence of antibiotics before, showed no great loyalty to their plasmids. After nine days in an antibiotic-free environment, the fraction of Klebsiella still harboring a plasmid dropped to less than 50%. For E. coli, less than 20% kept their plasmid.

When the researchers exposed the strains to antibiotics, growing each for 400 generations in their respective antibiotic, the strains showed greater affinity for their plasmids even after the antibiotic threat was lifted. After nine days in an antibiotic-free growth medium, more than half of E. coli and Klebsiella cells held on to their respective plasmid.

"Of course, the cells needed their plasmids to help them survive the antibiotic exposure. But even after we took away that selective pressure, both strains retained their plasmids at significantly higher levels than they had before the antibiotic exposure," said Jordt.

In addition, other experiments showed that antibiotic exposure increased the occurrence of MDR Klebsiella. Even without exposure to antibiotics, Klebsiella pneumoniae can acquire multiple plasmids. For example, when the researchers grew antibiotic-naive Klebsiella and E. coli plasmid-bearing strains together, a small fraction of Klebsiella became MDR by retaining their chloramphenicol-resistance plasmid and acquiring tetracycline-resistance plasmids from E. coli. But when the researchers repeated the experiment using antibiotic-exposed bacteria, they found roughly 1,000 times more MDR Klebsiella.

Prior prolonged exposure to just one antibiotic -- chloramphenicol -- had increased the likelihood that chloramphenicol-resistant Klebsiella would acquire the tetracycline-resistance plasmid from E. coli in an antibiotic-free environment. In addition, the team's experiments also showed that, when MDR cells were grown later in an antibiotic-free environment, chloramphenicol-exposed Klebsiella more readily held on to both resistance plasmids.

Evolution can explain both the persistence of the antibiotic-resistance plasmids and the increase of MDR in Klebsiella, the researchers say: Exposing the strains to their respective antibiotic selected for mutations in their genomes to minimize the clash between plasmid and host, making it less costly to keep that plasmid as well as others.

"We believe that by stabilizing one plasmid, these mutations make them more likely to stabilize additionally acquired plasmids," said Kerr.

Additional experiments may identify the specific mutations that helped E. coli and Klebsiella keep their plasmids, and why Klebsiella was more able to develop into a MDR strain than E. coli. Even though antibiotic exposure creates selective pressure to keep plasmids and acquire new ones, there is still widespread variation in how different species keep, share and receive plasmids.

"There are many, many details to be worked out in the future," said Top. "But what we see here is that even short-term exposure to just one antibiotic accelerates the development of multidrug resistance, which should give us pause as we use these drugs in health care, agriculture and other settings."

###

Co-authors on the paper are UW doctoral student Olivia Kosterlitz; Thibault Stalder, a research scientist at the University of Idaho; and José Ponciano, an associate professor of biology at the University of Florida. The research was funded by the National Institutes of Health and the National Science Foundation.

For more information, contact Kerr at kerrb@uw.edu and Top at evatop@uidaho.edu.

Grant numbers: R01 AI084918, DBI-0939454, T32GM007270, DGE-1762114, DEB-0952825

Link to full release with images: https://www.washington.edu/news/2020/04/27/antibiotic-exposure-mdr-bacteria/

Media Contact

James Urton
jurton@uw.edu
206-543-2580

 @UW

http://www.washington.edu/news/ 

James Urton | EurekAlert!
Further information:
https://www.washington.edu/news/2020/04/27/antibiotic-exposure-mdr-bacteria/
http://dx.doi.org/10.1038/s41559-020-1170-1

More articles from Life Sciences:

nachricht Rising water temperatures could endanger the mating of many fish species
03.07.2020 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Moss protein corrects genetic defects of other plants
03.07.2020 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

 
Latest News

Rising water temperatures could endanger the mating of many fish species

03.07.2020 | Life Sciences

Risk of infection with COVID-19 from singing: First results of aerosol study with the Bavarian Radio Chorus

03.07.2020 | Studies and Analyses

Efficient, Economical and Aesthetic: Researchers Build Electrodes from Leaves

03.07.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>