Abstract
We report the discovery of a simple environmental sensing mechanism for biofilm formation in the bacterium
Bacillus subtilis that operates without the involvement of a dedicated RNA or protein. Certain serine codons, the four TCN codons, in the gene for the biofilm repressor SinR caused a lowering of SinR levels under biofilm-inducing conditions. Synonymous substitutions of these TCN codons with AGC or AGT impaired biofilm formation and gene expression. Conversely, switching AGC or AGT to TCN codons upregulated biofilm formation. Genome-wide ribosome profiling showed that ribosome density was higher at UCN codons than at AGC or AGU during biofilm formation. Serine starvation recapitulated the effect of biofilm-inducing conditions on ribosome occupancy and SinR production. As serine is one of the first amino acids to be exhausted at the end of exponential phase growth, reduced translation speed at serine codons may be exploited by other microbes in adapting to stationary phase.
Bacteria use several different mechanisms to recognize and respond to changes in their environment. Protein sensors, for example, relay signals from the cell surface to target molecules within the cell. Additionally, RNA sensors can respond to internal levels of chemicals by regulating the expression of genes. Now, Subramaniam et al. have discovered a sensing mechanism in bacteria that does not rely on either protein sensors or RNA sensors.
Bacteria normally live as free swimming cells in water. But sometimes, in response to certain environmental conditions, they form a multicellular community called a biofilm. In this biofilm, bacteria encase themselves with layers of carbohydrates and proteins, which then protect the bacteria from adverse chemicals such as antibiotics. A protein known as SinR plays a key role during biofilm formation in the model bacterium Bacillus subtilis. SinR normally prevents the formation of the carbohydrates and proteins that make up the biofilm. Upon the decision to form a biofilm, B. subtilis counters the effect of SinR by producing an anti-SinR protein called SinI. Now Subramaniam et al. have found that as well as producing the SinI protein, B. subtilis use an additional mechanism to promote biofilm formation. This mechanism relies on codons, the elements within genes that correspond to specific amino acids. Six different codons correspond to the amino acid serine, and the gene for the SinR protein contains above average numbers of four of them. These four codons are highly sensitive to serine levels, and they decrease the levels of the SinR protein when there is less serine in the environment, as happens to be the case in biofilms. And since SinR prevents the production of the carbohydrates and proteins that make up the biofilms, a decrease in the levels of SinR leads to an increase in the production of biofilms. Since the serine codons at the heart of the sensing mechanism discovered by Subramaniam et al. are present in all forms of life, from viruses to humans, it is possible that similar sensing mechanisms might be found in contexts other than bacterial biofilms, such as in viral infection and cancer.