Keeping a step ahead of immunity.

Keeping a step ahead of immunity

The most powerful attribute of the human immune system is its ability to custom-tailor antibodies to attack a wide variety of invaders. But some troublesome microbes keep a jump ahead of the immune system by changing their surface characteristics more rapidly than the body can mount an attack -- and much more rapidly than medical researchers can devise new vaccines. Now biologists report that the mechanism underlying surface changes of at least one species of bacterium closely resembles the very mechanism the immune system uses to generate its wide range of antibodies.

Neisseria gonorrhoeae, the bacterium responsible for gonorrhea, often has hairlike structures called pili, which help attach it to a human cell during infection. Each pilus comprises a stack of many copies of a single "pilin" protein. But that protein is quite variable within a strain.

The pilin protein, like an antibody molecule, can be divided into regions that are constant (invariant), characterized by single amino acid changes (semivariable) and characterized by larger insertions and deletions (hypervariable). Magdalene So and her colleagues at the Scripps Clinic and Research Foundation in La Jolla, Calif., report that these regions are encoded in gene segments at different "silent" locations in the bacterial DNA. Before pilin protein is produced, a set of these segments must be brought together at one of the two "expression" sites in the DNA.

"This arrangement of constant and variable pilin sequences is reminiscent of that of immunoglobulin [antibody] gene segments," the scientists say in the April PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (No. 7). "To our knowledge, this complex assembly of genetic information has not been observed in prokaryotes [bacteria] until now." However, recent work indicates the same mechanism underlies surface changes of protozoan Trypanosoma equiperdum, which causes a venereal disease in horses.

In changeability, N. gonorrhoeae may have an advantage over the immune system. To bring together the appropriate segments of an immunoglobulin gene, a white blood cell snips out the intervening DNA, producing a permanent rearrangement. All cells that are descendants of an antibody-producing cell make the same antibody.

But the bacterium appears to rearrange its DNA in a more reversable manner, known as multiple recombination. Therefore a bacterium with pili can be the progenitor to bacteria with different pilin proteins.