University of Washington: Prolonged Antibiotics Use Could Make Bacteria Multidrug-Resistant

A new study by researchers at the University of Washington suggests that the use of antibiotics for an extended period could make bacteria that are resistant to a single antibiotic to be resistant to more drugs.

The study was reported in a paper that appeared recently in the journal Nature Ecology & Evolution.

Antibiotics help to deal with a wide variety of infections. With their help, medical experts are able to save millions of lives every year.Antibiotics Resistance

However, excessive use is contributing to the rising incidence of resistance by pathogens. There is even fear that the world may soon not have useful treatments for certain infections as a result.

The U.S. Centers for Disease Control and Prevention (CDC) estimates that around 2.8 million people in the country develop infections with bacteria that are resistant to antibiotics every year. Such infections result in over 35,000 deaths annually, according to the agency.

Doctors typically find multidrug-resistant (MDR) bacteria knottier to deal with.

Now, researchers from the University of Washington have found that protracted use of antibiotics can increase resistance. They discovered this in collaboration with colleagues from the University of Idaho.

The team observed that bacteria already resistant to a drug can develop resistance to another as a result of this. Prolonged antibiotic exposure of already-resistant bacteria “primes” them to increase the odds of picking up resistance to more antibiotics. This remains so even when they are no longer exposed to the antibiotics.

Studying bacteria response to antibiotics

For their research, the scientists focused on plasmids. These DNA strands are central to the ability of bacteria to develop resistance. They contain genes that are useful to these organisms, including those for warding off the effects of antibiotics.

Past research, however, shows that bacteria can easily dispose of plasmids. This is due to how they can get in the way of some key processes, including metabolism.

The research team in the current study explored plasmids in E. coli and Klebsiella pneumonia cells. These were resistant to tetracycline and chloramphenicol respectively.

These bacteria had previously not been exposed to antibiotics, so they more readily shed plasmids. The researchers kept them in an environment without any antimicrobial substance for nine days. Lower than 50 percent of Klebsiella cells still contained a plasmid after that time. E. coli cells still having the DNA strands dropped to less than 20 percent of the total.

Scientists then exposed the cells to antibiotics. They grew them for 400 strain generations in either tetracycline or chloramphenicol before keeping them in an antibiotic-free condition for nine days. More than 50 percent of cells in each bacterial group retained their plasmids in the absence of antibiotics.

The study showed that the strains rely on their plasmids as a means of surviving exposure to antibiotics.

Evolution and resistance

The research team further showed that prolonged exposure can make bacteria to evolve and become more resistant. It found that this can occur even when there is no longer antibiotic exposure.

The scientists grew together strains of E. coli and Klebsiella that are antibiotic-naïve and contain plasmids. Afterward, they observed that some of the latter have acquired plasmids resistant to tetracycline while retaining their own plasmids that are resistant to chloramphenicol. In other words, some Klebsiella cells became multidrug-resistant.

Next, the team repeated the experiment – this time with pathogens that had been exposed to antibiotics. They observed around 1,000 times increase in the number of Klebsiella cells that became MDR.

An additional experiment in an antibiotic-free condition showed that more MDR Klebsiella cells refused to shed their plasmids. They maintained their resistance to both drugs even when there is no threat of antibiotics.

The researchers said that evolution in the strains may explain why they become resistant to antibiotics and acquire multidrug resistance. Genome mutations make it less harmful for the bacteria to hold on to plasmids.

“We believe that by stabilizing one plasmid, these mutations make them more likely stabilize additionally acquired plasmids,” said Benjamin Kerr, a senior study author and professor of biology at the University of Washington.

There is still a need for future research to better understand how different bacteria share, keep, and acquire plasmids, the scientists said.

References

https://www.nature.com/articles/s41559-020-1170-1

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