They often live peacefully in our noses, but once Staphylococcus bacteria get under our skin, watch out for toxic shock, blood poisoning, or deadly infections. Now a team has unraveled the complete genetic codes of two dangerous strains, taking a step toward finding new treatments for these infections.
Keiichi Hiramatsu of Juntendo University in Tokyo and colleagues describe their analyses of the genetic codes in the 21 April issue of The Lancet. Hiramatsu's team is the first to determine the order of the bases that make up the genetic code of Staphylococcus aureaus, which is carried by one in three people across the globe. Another four strains are being sequenced by publicly funded laboratories and at least two by companies, making this the most sequenced microbial genome yet.
Hiramatsu and colleagues chose to sequence one totally antibiotic-resistant strain, called Mu50, that was obtained in 1997 from a baby's infected surgical wound. For comparison, they also sequenced the genome of a second, related strain--N315, isolated in 1982--that resisted most antibiotics but was still susceptible to vancomycin, often considered the antibiotic of last resort.
The S. aureaus genome turns out to be a mosaic of foreign and native DNA, the group reports. At least 18 genes appear to come from other species of bacteria or other organisms--a few possibly even from humans. And distributed throughout each microbe's chromosome are many bits of mobile DNA, snippets that can jump from one part of the genome to another. This footloose DNA differs from strain to strain. For example, when the analysis turned up 2595 tentative genes for the N315 strain and 2697 for Mu50, the researchers found that many of those extra genes are in mobile elements found only in the Mu50 genome. These mobile elements and other extraneous DNA are what make these strains dangerous to humans and help them resist killing by antibiotics.
Why do these two strains cause so many problems in people? The analysis turned up new candidate danger spots in the genomes. The researchers found 70 never-before-seen genes that, based on their resemblance to other known genes, look to be involved in making these strains virulent. These include three new types of "pathogenicity islands," stretches of DNA with multiple genes that promote infection or stimulate immune responses in people.
These new genomes are "a major step in understanding how this organism causes disease," says John Iandolo, a microbiologist at the University of Oklahoma, Oklahoma City.