Why Do Some Infections Persist? Blame Bacterial Socialism, Says New Study

The diverse colors at the opening of the video show the range of antibiotic resistance in the bacterial community. The more cyan-hued the cells are, the greater their resistance. After an antibiotic is introduced, the most cyan-colored cells ‘filament,’ turning into elongated tubes, as a way of surviving the antibiotic. The darker cells, which had the least antibiotic resistance, die, as shown by a red dye indicating cell death. After the antibiotic disappears, the filamented cells will return to normal growth via dividing. This research finding has important implications for antibiotic dosing strategy to most effectively fight infections.

In preparing for the possibility of an antibiotic onslaught, some bacterial cultures adopt an all-for-one/one-for-all strategy that would make a socialist proud, University of Vermont researchers have found. 

This finding, published Jan. 13 in the journal Scientific Reports, could have application for how persistent infections like those associated with cystic fibrosis are treated.

The paper’s conclusions are based on a series of time-lapse videos showing that single cells within a community of bacteria randomly use a cascade of proteins to become more or less antibiotic resistant, even when the community is not threatened by an antibiotic. A bacterial colony can regenerate if only a few cells survive antibiotic treatment.

The paper’s lead author is Imane El Meouche, a postdoctoral scholar in the School of Engineering in the College of Engineering and Mathematical Sciences. Mary Dunlop, corresponding author, is an assistant professor in the School of Engineering. The second author is Yik Siu, a technician in the school.  

“It’s costly from a metabolic standpoint for a cell to express the proteins that enable it to be resistant,” says Dunlop. “This strategy allows a colony to hedge its bets by enabling individual cells within a population to trade back and forth the work required for antibiotic resistance. That way the population will be prepared for an antibiotic threat, should one arise, but without doing the extra work that could put it at risk in other ways.”

Previous research has demonstrated that, when exposed to some antibiotics, all the cells within a bacterial population will use the protein cascade strategy, activated by a mechanism called MarA, to become resistant.

But the new study is among the first to show that colonies use the strategy even when they are not under threat.

“This transient resistance, distributed in varying degrees among individual cells in a population, may be the norm for many bacterial populations,” Dunlop says.

Clinical implication: Change dosing strategy to wait out an infection

That may explain why infection persists in diseases like cystic fibrosis, she said. For these diseases, clinicians know not to use antibiotics that will stimulate population-level MarA resistance.

But the persistence of a few straggler antibiotic-resistant cells, even after treatment with the right antibiotic, could be enough to keep the infection alive.

The study suggests that altering the frequency and timing of antibiotic treatment could be a way of waiting out an infection as bacteria trade off antibiotic resistance, enabling the drug to kill the entire culture.

Some antibiotic-resistant bacteria, such as MRSA, are resistant due to genetic changes such as mutations. Those studied by Dunlop and her colleagues alter their traits – protein expression, for instance – but not their genomes, making them significantly more difficult to identify since the resistance level of each bacterium changes over time.