��ñ��

Communities of bacteria known as biofilms play a major role in hard-to-treat infections that can ruin lives.

To spread, these cells must leave the slimy biofilm matrix and revert to a solitary, planktonic state. A new paper by ��ñ�� Distinguished Professor of Biological Sciences Karin Sauer and postdoctoral researcher Manmohit Kalia in the journal mSphere explores this transitional state — with some surprising findings.

The article, “Distinct transcriptome and traits of freshly dispersed Pseudomonas aeruginosa cells,” focuses on a bacteria well-known for causing infections in healthcare settings, in connection with ventilators, the lungs of cystic fibrosis patients, burn wounds and more. In it, Sauer and Kalia find that dispersion seems to constitute a state of its own, with cells expressing genes differently than in their biofilm or mobile condition.

“Dispersion enables bacteria to actively leave the biofilm and return to the planktonic, single-cell mode of growth. However, the cells that disperse from the biofilm do not behave like planktonic cells,” Sauer said.

Planktonic cells are up to a thousand times more susceptible to antibiotics than the same bacterium grown as a biofilm, Sauer pointed out. This heightened tolerance is the reason that conventional antibiotic treatment can fail in chronic, biofilm-related infections.

Previously, dispersed cells were considered as susceptible to antibiotics as planktonic cells, but the situation is more complex.

“There is increasing evidence that the susceptibility of dispersed cells is variable and, depending on the antibiotic, dispersed cells have been reported to be as tolerant as biofilms or as susceptible as planktonic cells,” she said.

This changed state may allow the cells to adapt to new environments while avoiding the host’s immune system — a survival trait, when seen from the cell’s perspective.

Leaving the biofilm

Researchers know of several chemical signals that can trigger cells to actively disperse from a biofilm. They include nitric oxide and cis-2-decenoic acid, whose role in dispersion was discovered by ��ñ�� Professor David Davies; other signals include an increase in nutrient concentration, pH changes and oxygen limitation.

There are other, passive ways to disassemble biofilms, which generally involve degrading the slimy matrix surrounding the bacteria, Sauer said.

Changes in gene expression and phenotype were detectable within minutes of the dispersed cells leaving the biofilm. Kalia and Sauer reference prior research indicating that the distinct phenotype of dispersed cells is still detectable 5 hours post-dispersion, but that prior study made use of dispersed cells in the presence of the dispersion inducer. The effect of the dispersion inducer on the cells over time is also unknown.

“But since this is such a great question, we have already started looking into it and are currently finishing a manuscript,” Sauer said.

Dispersion is being discussed as a viable option for the eradication of biofilm-related infections, since it’s a promising avenue to reduce the size of the biofilm and increase the susceptibility of the remaining biofilm cells to antibiotics. However, there is also evidence that dispersion can cause bacteremia, or the presence of bacteria in the blood, which some have likened to Pandora’s box, Sauer pointed out.

“I believe that much of the discussion on dispersion — viable option or not — is fueled by a lack of understanding what dispersed cells are, how they behave, and how they differ from planktonic and biofilm cells,” she said. “Our findings provide a detailed characterization of dispersed cells that we hope will enhance our understanding of how to best use dispersion as an anti-biofilm strategy, and what precautions need to be taken to prevent dispersion and dispersed cells from overwhelming the immune system.”