What determines how big or small bacteria are? New research from Washington University in St. Louis shows that fat makes bacteria fat. Makes sense.
The researchers, led by Petra Levin, knew that nutrient starvation made bacteria shrink in size by up to 3-fold. Here, they show that fatty acid biosynthesis is a key regulator of cell size in E. coli, B. subtilis, and even S. cerevisiae.
First, they investigated which biosynthetic pathways most affected cell size. They grew E. coli in nutrient-rich broth with subinhibitory concentrations of rifampicin to decrease RNA synthesis, chloramphenicol to decrease protein synthesis, and cerulenin to decrease fatty acid synthesis. They found that only cerulenin - the inhibitor of fatty acid synthesis - decreased cell size and growth in the same way that nutrient limitation did.
They reasoned that fatty acids determined cell size because some fatty acids are used to make the plasma membrane - the membrane that encloses all the cell’s contents. The idea was that if you can add more fatty acids to the membrane, you can make the cells larger.
To test this, they grew a specific set of mutants with oleic acid - a fatty acid that the bacteria could incorporate into their membranes. The oleic acid rescued the growth defect of fadE mutants - these mutants cannot use fatty acids as a carbon source. On the other hand, the oleic acid did not rescue the growth defects of fadL or fadD mutants - these mutants cannot incorporate fatty acids into the plasma membrane. These results suggest that the growth and size defects stem from the inability to incorporate fatty acids into the membrane.
Next, the researchers wondered whether their findings applied to other bacteria and even eukaryotic cells.
They found that cerulenin - the fatty acid synthesis inhibitor - also decreased the size of B. subtilis and S. cerevisiae cells. As for E. coli, the addition of oleic acid helped rescue the growth rate and size defects in B. subtilis and S. cerevisiae.
Finally, they reasoned that if reducing fatty acid synthesis reduced cell size, then increasing synthesis should increase cell size. When they overexpressed fadR in E. coli - a regulator that increases fatty acid synthesis - the cells doubled in size.
This research should remind us that lipids are pretty darn important. According to study author Stephen Vadia, "people don't think about lipids. It probably goes back to the central dogma of biology that we're all taught: DNA makes RNA makes protein, and proteins do everything. Lipids have been regarded as a sideshow."