Amino acids—the building blocks of proteins—are chiral molecules, which means they can exist in two mirror forms. While L-forms of amino acids are predominantly found in nature, the D-forms are less abundant and little is known about their biological function. But new research shows that the few D-amino acid outliers play a vital role in regulating cell wall growth in bacteria.
Matthew K. Waldor, an HHMI investigator at Brigham and Women's Hospital, was studying how Vibrio cholerae, the bacterium that causes cholera, gets its characteristic rod shape. His lab identified a mutant that became spherical when cultured overnight. Waldor's team suspected that something was accumulating in the culture that affected the mutant bacterium's shape. They analyzed the chemicals floating in the soup around the bacteria and found a plethora of right-handed, or D-amino acids.
“This was really amazing,” says Waldor. “No one even knew that bacteria make these types of D-amino acids, and not only were they there, they were there in high concentrations.”
The cell wall of most bacteria, including V. cholerae, consists of a complex of molecules called peptidoglycans and is separated from the watery cytoplasm of the cell by an inner membrane. Scientists have puzzled over how the inside of the cell coordinates growth with the cell. Waldor's group found that D-amino acids are chemical signals that can downregulate cell wall metabolism when bacteria slow their growth.
His lab group pinpointed an enzyme, called a racemase, that V. cholerae uses to create certain D-amino acids and mutated it to test the effects. Without D-amino acids, the cell wall's growth was uncoordinated with the cell's inner growth. The team's findings were published in Science on September 18, 2009.