Looking closer at bacteria to end their resistance

IU researchers learn about DNA-reeling bacteria with new imaging method, which should aid in efforts to better understand how superbugs acquire drug resistance

Jeffrey Bouley
Register for free to listen to this article
Listen with Speechify
BLOOMINGTON, Ind.—Bacteria gaining antibiotic resistance has been a problem for some time and poses ever-increasing dangers to human health. With relatively little work being done in the area of engineering new antibiotics, gaining a better understanding of how bacteria acquire this resistance could be key to better fighting it and better focusing the development of future antibiotics.
Recently, some progress was made on this front thanks to researchers at Indiana University (IU) who developed a new imaging method allowing them to see for the first time how bacteria use their long and mobile appendages—called pili—to bind to, or “harpoon,” DNA in the environment, “like a fisherman pulling up a catch from the ocean,” according to IU, which also noted, “The act of gobbling up and incorporating genetic material from the environment—known as natural transformation—is an evolutionary process by which bacteria incorporate specific traits from other microorganisms, including genes that convey antibiotic resistance.”
This new ability to image the bacterial activity also revealed a previously unknown role a protein plays in helping bacteria reel in DNA, which might lead to new ways of stopping bacterial infection. The IU team’s findings were reported Oct. 18 in the journal PLOS Genetics.
“The issue of antibiotic resistance is very relevant to this work since the ability of pili to bind to, and ‘reel in,’ DNA is one of the major ways that bacteria evolve to thwart existing drugs,” noted Dr. Ankur Dalia, an assistant professor in the IU Bloomington College of Arts and Sciences’ Department of Biology, who is senior author on the study. “An improved understanding of this ‘reeling’ activity can help inform strategies to stop it.”
Although they may look like tiny arms under a microscope, Dalia said, pili are actually more akin to an erector set that is quickly put together and torn down over and over again. Each “piece” in the structure is a protein sub-unit called the major pilin that assembles into a filament called the pilus fiber.
“There are two main motors that had previously been implicated in this polymerization and depolymerization process,” added Jennifer Chlebek, a Ph.D. student in Dalia’s lab, who led the study. “In this study, we show that there is a third motor involved in the depolymerization process, and we start to unravel how it works.”
The two previously characterized “motors” that control the pili’s activity are the proteins PilB, which constructs the pili, and PilT, which deconstructs it. These motors run by utilizing ATP, a source of cellular energy. In this study, IU researchers showed that stopping this process, which switches off the power to PilT, does not prevent the retraction of the pili, as previously thought.
Instead, they found that a third motor protein, called PilU, can power pilus retraction even if PilT is inactive, although this retraction occurs about five times more slowly. The researchers also found that switching off power to both retraction proteins slows the retraction process to a painstaking rate of 50 times slower. An unaltered pilus retracts at a rate of one-fifth of a micron per second.
Moreover, the study found that switching off PilU affects the strength of pilus retraction, which was measured by collaborators at Brooklyn College. The study also showed that PilU and PilT do not form a “hybrid” motor, but instead that these two independent motors somehow coordinate with one another to mediate pilus retraction.
Next, Chlebek aims to learn more about how the pili still retract when the power is switched off to both retraction motors, as well as explore how these insights could apply to understanding pili activity in other strains of bacteria.

Jeffrey Bouley

Subscribe to Newsletter
Subscribe to our eNewsletters

Stay connected with all of the latest from Drug Discovery News.

March 2024 Issue Front Cover

Latest Issue  

• Volume 20 • Issue 2 • March 2024

March 2024

March 2024 Issue