A ‘weak spot’ in the cell wall emerges as bacteria build tails for movement, offering a potential path to overcome antibiotic resistance

Researchers have found for the first time that building the tails bacteria use for movement puts stress on the cell wall, and that bacteria have a system to ease that stress. The finding could offer a clue to new strategies for treating infectious diseases as antibiotic-resistant bacteria become more common.

According to Indiana University on the 10th local time, a research team led by Daniel Kearns, a professor in the university’s Department of Biology, identified a mechanism in which the cell wall is damaged during bacterial flagellum formation and then repaired. The findings were published in the Proceedings of the National Academy of Sciences (PNAS).

The study was co-led by researchers Caroline Dunn and Kehinde Adebiyi, who conducted experiments on Bacillus subtilis, a harmless soil bacterium. Many disease-causing bacteria, including Escherichia coli, Salmonella and Listeria, use flagella to move through the body, invade tissues and spread infection.

To build a flagellum, bacteria must push several components through the cell wall, which is made of peptidoglycan. The researchers expected that removing PBP1, a protein that repairs small gaps in the cell wall, would create more openings for flagella to pass through.

Instead, when PBP1 was removed, bacteria began dying in large numbers, and the timing of their deaths precisely matched the period of flagellum formation. “I expected flagellum assembly to be less regulated when we removed PBP1, but I didn’t expect it to be lethal,” Dunn said. “When we saw the cells burst as soon as the flagella were made, we knew we had found something that hadn’t been seen in this field.”

Genetic experiments showed that once a component of the flagellum called the “hook” is complete, a genetic switch inside the bacterium activates enzymes that break down the cell wall. This breakdown helps the flagellum take its proper position and rotate, but it also causes damage; PBP1 repairs that damage immediately, maintaining the cell wall, the researchers explained.

Without PBP1, the cell wall breaks down faster than it can be repaired, causing the bacteria to burst and die. “It’s interesting that a structure considered only a means of movement can actually create a vulnerability in the bacterial cell envelope,” Adebiyi said. “This shows that flagellum assembly and cell wall maintenance are much more closely connected than previously known.”

The researchers wrote in the paper that flagella “have generally been considered not to affect cell survival, but they can be toxic to the cells that make them.” The discovery suggests that similar risks may arise when disease-causing bacteria build structures that must pass through the cell wall, such as tools for injecting toxins.

The researchers hope that targeting this vulnerability could lead to drugs that prevent bacteria from making the tools they need to move and invade. The study was supported by the National Institutes of Health (NIH).