The ability of bacterial cells to hunker down as resilient biofilms is an important mechanism used to respond to stress. So is the ability to swim away from a nutrient-poor or stressful environment (for those bacteria lucky enough to be motile). Stay versus go: it’s a primal precursor to fight-or-flight decisions. But as single-celled organisms, bacteria don’t ‘decide’ to initiate biofilm formation versus motility machinery – so how do these cells determine which behavior to commence?
New research published in the Journal of Bacteriology suggests a link between these programs. Scientists in Dr. Simon Dove’s lab study Pseudomonas aeruginosa, a soil-dwelling bacterium that causes opportunistic infections. This bacterium both causes hard-to-treat biofilms and has several modes of motility, including swarming motility. This swarming motility can be observed after inoculating a small colony on an agar plate; after a few days, the bacteria will have expanded in a swirling pattern as they search for nutrients. These behaviors are inversely correlated, and this new data suggests they are reciprocally regulated.
A previous high-throughput study had identified sbrR as a P. aeruginosa gene needed for respiratory infection – a common type of infection caused by P. aeruginosa. In this new research, scientists recognized the gene, sbrR, was part of a two-gene operon together with sbrI (named after this research was conducted). While no functional homology was recognized with sbrR, sbrI had sequence similarity to other σ factors, a class of genes whose products interact with RNA polymerase to direct bacterial transcription.
The authors first demonstrated that SbrI interacts with RNA Polymerase (as a predicted σ factor would). Suggested by consistency of the genomic arrangement of sbrR and sbrI with other systems, the authors then hypothesized that sbrR is an anti-σ factor. Anti-σ factors negatively regulate σ factor activity; without them, the σ factor can become constitutively active.
What does this mean for motility versus biofilm formation? When the researchers generated a mutant ΔsbrR strain, they observed complete lack of swarming motility (see figure, right). One of the genes activated by SbrI is called muiA. In the ΔsbrR mutant strain, SbrI hyperactivity leads to 100 times more expression of this transcript. Another gene without significant homology, the researchers thought muiA overexpression might explain the swarming defect. By knocking out muiA in the ΔsbrR strain, the scientists rescued bacterial swarming – demonstrating that MuiA is somehow inhibiting this behavior.
Swarming behavior might not seem innately applicable to human health, but biofilms certainly are. Many hospital-acquired P. aeruginosa infections originate from biofilms on indwelling devices such as catheters and ventilators. And biofilm formation is a trait associated with successful virulence – sbrR was originally identified in a screen for chronic respiratory infection, to which its enhanced biofilm formation (also shown in the current paper) may have contributed.
There’s still a lot to learn about this system, of course: What does MuiA actually do that inhibits swarming? Does MuiA impact biofilm formation? How does SbrI activation vary at the cellular and at the colony level? As we better understand how bacteria ‘decide’ their behavior, scientists are better able to manipulate these genetic circuits to suppress virulence, with the long-term goal of improving human health.
-- Julie Wolf