Single Gene May Defend Bacteria From Antibiotics And Infection

Streptococcus pyogenes bacteria are behind a number of infections, such as sore throats and skin infections, and are even the culprits behind necrotizing fasciitis, the so-called “flesh-eating bacteria.” But as scientists tried to track the bacteria’s movements by comparing samples from different infections, they noticed a growing resistance to macrolide antibiotics, a class of drugs often prescribed to patients who are allergic to penicillin. The new research suggests that a new gene in these resistant bacteria, called spyIM, may be the key to the bacteria’s drug resistance.

Scientists track infections by comparing the genomes of different bacteria in order to understand how the different strains causing these infections have spread and changed. As in the case of S. pyogenes, this is often done by cutting up their genomes with a restriction enzyme called SmaI, which slices a bacteria’s DNA into predictable pieces. Any differences or similarities in number and size of the pieces help researchers see how bacteria from different places are related. “But a number of studies have reported that DNA from a diverse group of resistant S. pyogenes could not be cut by SmaI,” says senior author Vincent Fischetti, head of the Laboratory of Bacterial Pathogenesis and Immunology.

Fischetti’s lab found that all of these bacteria carried a new gene, which they named spyIM, that encodes an enzyme, M.SpyI, that places methyl groups on specific residues in the DNA. When the enzyme acts on the bacteria’s DNA, it changes it in a way so that SmaI can no longer cut it. “M.SpyI is the first methyltransferase enzyme from S. pyogenes to be cloned and actively characterized,” says Chad Euler, first author and graduate fellow in the Fischetti laboratory. “And it explains the inability of previous studies to analyze streptococcal DNA by SmaI.”

The research suggests that having this gene not only makes the bacteria resistant to antibiotics, but may also play a role in protecting S. pyogenes from infection by bacteriophages. The infecting viral DNA would not be methylated by M.SpyI like the bacterial DNA, so it would be vulnerable to being cut by the bacteria’s own restriction enzymes. The spyIM gene imparts an evolutionary advantage, and the result is an especially dangerous strain of bacteria: one that’s resistant to antibiotics it has never even been exposed to.

Citation: Journal of Bacteriology 189(3): 1044-1054 (February 2007)