New Hope For Fighting Antibiotic Resistance

The finding could aid future research into developing drugs that can skirt the potentially catastrophic problem of bacterial resistance to antibiotics. In a paper published April 23 in Proceedings of the National Academy of Science, Kenneth Bayles, Ph.D., of UNMC, writes that “programmed cell death” in bacterial communities is a form of altruism that benefits the larger community of cells and helps strengthen them.

“People get caught up in the idea that altruism is a behavior that requires deep thought, planning, and feelings such as caring,” Bayles said. But he argues through his research that altruism appears to be an innate function in cell death, or “lysis.”

Three years ago, Dr. Bayles, a professor of pathology and microbiology at UNMC, began growing cells in biofilm to observe how communication between cells – known as “quorum sensing” – affects their survival.

He observed that when cells are forming a biofilm – a colony of bacteria that contains resistant organisms and is involved in many antibiotic-resistant infections – they perform a function that enables them to leave a unique imprint on the world: their DNA. A small percentage of cells explode in a process called “lysis,” leaving behind a sticky residue that contains DNA and other cellular bioproducts which are then incorporated into the larger cell community to build a stronger biofilm.

“For a long time, microbiologists viewed bacteria as wholly simplistic organisms that lived alone and died alone,” said Dr. Bayles, noting that the discovery of “quorum sensing” nearly 40 years ago was a giant leap forward in understanding the complexity of communication and interaction between cells. “My research takes the concept to the extreme, with the idea that a fraction of the bacterial population actually dies for the good of the community.”

Dr. Bayles’ hypothesis could represent a paradigm shift in one of the cornerstones of microbiology, because understanding how cells die naturally – or how they commit “suicide” – could yield entirely new ways of killing them clinically. Previously, programmed cell death has been observed only in higher species.

He compares the process to what happens in a colony of honeybees or ants, which share 75 percent of their DNA. If something endangers one of them, a few others react altruistically – stinging intruders to defend the colony. “Sting once, and you’re dead, but it’s for the good of the colony,” Dr. Bayles said. Because bacteria in a biofilm share 100 percent of their DNA, their “suicide mission” is more pronounced; instead of just a few cells dying, many die and leave behind their DNA, thus strengthening the survivors.

Researchers have struggled with the question of why biofilms are extremely resistant to antibiotic drugs. “We don’t know why, but we think it’s because the cell death function is suppressed in the cells that don’t commit suicide, making them tolerant to antibiotics,” Dr. Bayles said. “In biofilm infections, if we can turn the cell death function back on, we can make them less resistant to antibiotics. Our research uncovers new targets for antibiotics, which we desperately need.”

Programmed cell death in mammals is a major topic in cancer research, and Bayles said his findings could potentially aid researchers trying to develop cancer drugs.

Bayles’ findings are bound to be controversial, because he assigns a highly intellectual characteristic to these bacterial cells, although he says this altruistic behavior is likely an innate function.

“This has been brewing for the past 15 years, but now we’ve made this leap and we can say we’ve seen programmed cell death in biofilm,” Dr. Bayles said. “Some microbiologists have been slow to accept that programmed cell death makes sense in bacteria because they are single-celled, but many are now coming around to the idea.”