Study Finds How Bacteria Evolve To Become Antibiotic Resistant

The mechanism by which bacteria adapt is profoundly intimidating. Expose them to antibiotics, they’ll evolve rapidly, develop resistance to antibiotics and make ordinary infections extremely difficult to deal with. But how do we ever thwart the lunacy of these mindless little critters. Well, we might just have figured a way out.

For the first time ever, a team of researchers from Indiana University have observed one of the fundamental processes by which bacteria rapidly evolve to become antibiotic resistant. According to researchers, understanding the exact mechanism they use to rapidly evolve new traits, develop antibiotic resistance and how they share DNA can help us concoct ways to restrain them from evolving, and therefore stopping them from developing resistance to antibiotics.

To figure out how bacteria evolve, the team invented a method to record images of bacterial appendages — over 10,000 times thinner than human hair – in an act of harpooning a piece of DNA. And through a process called DNA uptake or Horizontal Gene Transfer, these fragments of DNA is incorporated into their own genetic material for speedy evolution.

“Horizontal gene transfer is an important way that antibiotic resistance moves between bacterial species, but the process has never been observed before, since the structures involved are so incredibly small,” explained senior author Ankur Dalia, an assistant professor in the IU Bloomington College of Arts and Sciences’ Department of Biology.

“It’s important to understand this process, since the more we understand about how bacteria share DNA, the better our chances are of thwarting it,” he added.

These superfluously thin, hair-like appendages called pili are too difficult to be seen even under microscope. But, how did the researchers manage to catch sight of them in an act of snaring a piece of DNA. Well, here’s what they did.

In the study, researchers used Vibrio cholera, microbe responsible for cholera. Pili’s role in HGT is well established, however the evidence demonstrating how they work had remained intangible until this study.

In order to observe pili in action, researchers developed a new method of “painting” both the pili and DNA fragments with special glowing dyes. After they put them under the microscope, they were able to see pili act like a harpooners that cast a line through pores in the cell wall to grap a piece of DNA at the very tip, then reel the DNA back into the bacterial cell through the same opening that is so small that the DNA would need to fold in half to fit through it.

“It’s like threading a needle,” said Ellison, who is first author on the study. “The size of the hole in the outer membrane is almost the exact width of a DNA helix bent in half, which is likely what is coming across. If there weren’t a pilus to guide it, the chance the DNA would hit the pore at just the right angle to pass into the cell is basically zero.”

The next step is to study how pili clasp onto the DNA at exactly the right spot, especially considering the way the protein involved with the process interact with DNA – it’s like never seen before. The team also anticipates the use of the same dyeing method to explore other functions by pili.  

“These are really versatile appendages,” said Dalia. “This method invented at IU is really opening up our basic understanding about a whole range of bacterial functions.”

The study has been published in the journal Nature Microbiology