Antibiotics boost bacterial growth

Researchers at the University of Exeter exposed Escherichia coli (also known as E.coli) bacteria to eight rounds of antibiotic treatment over a period of four days.

In the process, the germs, which usually cause stomach pain and diarrhea and in worse cases kidney failure, increased antibiotic resistance with each treatment.

This was a mutation the scientists expected. What they were not prepared for was the observed speed with which the resistant germs multiplied after being treated. In one case the bacteria populations grew three times as big as in the case of normal E.coli bacteria within the same timeframe.

Bacterial mutants are sustainable

Even after removing the antibiotics, the mutated bacteria maintained its ability to multiply faster.

"Our research suggests, there could be added benefits for E.coli bacteria when they evolve resistance to clinical levels of antibiotics," lead author Prof. Robert Beardmore said. "It is often said that Darwin evolution is slow, but nothing could be further from the truth, particularly when bacteria are exposed to antibiotics."

He described the ability of bacteria to rearrange their DNA as "remarkable." This could stop drugs from working sometimes in a matter of days. "While rapid DNA change can be dangerous to a human cell, to a bacterium like E.coli it can have multiple benefits, provided they hit on the right changes."

Finding the source by DNA sequencing

As part of the study, which was published on January 30th 2017 in the journal Nature Ecology & Evolution, the scientists exposed the bacteria to the antibiotic doxicycline. Then, they froze the bacteria at minus 80 degrees Celsius and conducted gene sequencing to find out exactly which genetic changes were responsible for the observed resistance.

Some of the changes were well known and described in clinical patients. One of them is the ability of the bacteria to produce more "antibiotic pumps". These are segments called "pump DNA", which literally pump antibiotics out of the bacterial cell with the result of ensuring that the drugs can not do their work.

But the scientists also discovered that the mutated bacteria were lacking part of the DNA that is known to describe a dormant virus.

Several parallel evolutionary processes at work

What that means exactly is not clear, but Dr. Carlos Reding - a co-author of the study - has an idea. "Our best guess is that losing viral DNA stops the E.coli destroying itself, so we see more bacterial cells growing once the increase in pump DNA allows them to resist the antibiotic in the first place," Reding said. "This creates an evolutionary force for change on two regions of the E.coli genome".

Usually, bacteria tend to use self destruction as a means to colonize surfaces. That's how a biofilm develops - the slimy substance found, for instance, in the drains of sinks.

"But our study used liquid conditions, a bit like a bloodstream, so the E.coli could give up its biofilm lifestyle in favor of increasing cell production", the researcher suggests.

Using antibiotics in a targeted way

Dr. Mark Hewlett - also from Exeter University - added: "It is said by some that drug resistance evolution doesn't take place at a high dosage but our paper shows that it can and that bacteria can change in ways that would not be beneficial for the treatment of certain types of infection."

Anyhow, he concludes, that it is important to use "the right antibiotic on patients as soon as possible. So we don't see adaptations like these in the clinic."