Nav: Home

Evolution of efflux pumps could yield important insights in fighting antibiotic resistance

July 26, 2018

LAWRENCE -- Different types of efflux pump proteins -- which are the key focus of Gram-negative bacteria antibiotic resistance -- might have evolved independently instead of, as previously thought, all from a common ancestor, according to a new study led by a University of Kansas computational biologist.

The discovery could be crucial in future research advancing treatments to mediate antibiotic resistance of bacteria strains such as E. coli, Salmonella, Shigella, Meningococcus and others.

"Antibiotic resistance is all about evolution; it's about proteins evolving functions to allow the bacteria to survive and to ensure bacterial evolutionary success," said Joanna Slusky, KU assistant professor of molecular biosciences and computational biology. "By learning from nature, we can learn the evolutionary steps and then the question becomes, can we design proteins using evolutionary steps that will ultimately ensure our own genetic success?"

Slusky works on designing proteins that will re-sensitize bacteria to common antibiotics and on overcoming drug-resistant superbugs.

She was the lead author of the study published Thursday in the journal Structure. Co-authors include KU graduate students in computational biology, Meghan Franklin, and Ryan Feehan, who also served as a KU undergraduate research assistant in KU's Center for Computational Biology. Other co-authors are Sergey Nepomnyachiy and Rachel Kolodny, both of the Department of Computer Science of the University of Haifa, Mount Carmel in Israel as well as Nir Ben-Tal from the Tel Aviv University. Nepomnyachiy is also affiliated with the Department of Biochemistry and Molecular Biology at Tel Aviv University.

The researchers examined proteins called beta barrels that are in the bacterial surface. The study started by comparing most types of beta barrels with the beta barrels of efflux pumps. In efflux pumps the beta barrel forms the outer crown of the large pumps that push antibiotics out of the cell.

In examining the sequence-level variation of these beta barrels, the researchers discovered the beta barrels that were involved in antibiotic resistance lacked sequence linkage to other beta barrels and also had structural differences. This led them to conclude that the efflux pump beta barrels and the other beta barrels may not have divergently evolve from a common ancestor.

Instead the pressures of nature -- through convergent evolution -- may have forced bacteria to develop both types of barrel proteins separately.

"We went from saying, 'how are these related?' To saying, 'oh, we think they're not related, and what does having a different structure mean for the mechanism of antibiotic resistance?'" Slusky said.

It has been a challenge for scientists to document the homology of outer-membrane beta barrels because of the extreme bacterial sequence variation making proteins seem more different. Also, the counter influence of the high sequence similarity required for the strands of beta barrels makes proteins look more similar.

There are about 100 varieties of outer membrane proteins in each species of Gram-negative bacteria.

Slusky said there clearly is a need for bacteria to utilize efflux pumps to move certain compounds from the cell, but in the context of defeating drug-resistant superbugs they can hold a key piece of the puzzle.

"The efflux pumps are the very same pumps that we're trying to target to remediate antibiotic resistance," Slusky said.

The evolutionary process the researchers documented promotes the hypothesis that the beta barrels in the efflux pumps function similar to the iris of an eye that expands and contracts due to the level of light in a person's environment, she said.

"We're going to be looking out for this iris-like mechanism," Slusky said. "If this is the mechanism for antibiotic resistance, then the next question is, how do we disable that mechanism?"

As part of the paper, the researchers also found that autotransporters may be the best known models for the primordial outer-membrane beta barrel structure, giving biologists clues to how the beta barrel essentially became stitched together over time.

"Understanding evolution tells us where biology was, which is interesting to people because it tells us our own history and the earth's history," Slusky said. "But it also tells us where we could be going and what mechanisms are possible. It tells us how might life evolve and what tools can biologists use to change and diversity the molecules at our disposal."
-end-


University of Kansas

Related Bacteria Articles:

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.
Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.
Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.
Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.
Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.
How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.
The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?
Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.
Bacteria uses viral weapon against other bacteria
Bacterial cells use both a virus -- traditionally thought to be an enemy -- and a prehistoric viral protein to kill other bacteria that competes with it for food according to an international team of researchers who believe this has potential implications for future infectious disease treatment.
Drug diversity in bacteria
Bacteria produce a cocktail of various bioactive natural products in order to survive in hostile environments with competing (micro)organisms.
More Bacteria News and Bacteria Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.