Friday, December 19, 2008

How Superbug Staph aureus Resists Our Natural Defenses

Researchers at the University of Washington have uncovered how the bacterium Staphylococcus aureus, including the notorious MRSA (methicillin-resistant Staph aureus) "superbug" strains, resists our body's natural defenses against infection. The work, which was featured on the cover of the March 21 issue of Science, could lead to new ways to fight the bacteria.


Dr. Ferric Fang, UW professor of laboratory medicine and microbiology, and his UW colleagues Dr. Anthony Richardson and Dr. Stephen Libby set out to determine what makes Staph aureus a better pathogen than other bacteria. They focused on a chemical compound called nitric oxide (NO), a natural antibiotic that our cells excrete to protect us from pathogens. For most bacteria, NO creates an environment that keeps invading microbes from undergoing respiration or fermentation, vital chemical processes that allow bacteria to grow.

The researchers found that Staph aureus has a mechanism that allows it to produce lactic acid in the presence of NO, which allows it to maintain its chemical balance and keep growing and thriving in the harsh host environment. When Staph aureus is exposed to NO, it produces the novel enzyme responsible for lactic acid production, along with another enzyme that converts NO to non-toxic products. NO is commonly found in the nose and nasal passages, and is meant to protect people against disease-causing microbes. But Staph aureus is commonly found in the nose despite the presence of NO, the researchers explained.

When the researchers modified Staph aureus to take away its ability to make lactic acid, the bacteria could no longer tolerate NO. The modified bacteria also lost their ability to survive in host immune cells and cause lethal disease in mice.

"MRSA has become an enormous public health problem, by causing both hospital- and community-acquired infections," explained Fang. "Staph aureus has already colonized about one-third of the world's population, so traditional antibiotics will probably not be the complete answer to the MRSA problem."

However, the researchers added, trying to make Staph aureus more susceptible to our natural defenses might lead to new strategies to de-colonize the population and prevent staphylococcal infections.


Wednesday, December 17, 2008

Fungi Can Tell Us About The Origin Of Sex Chromosomes

Fungi do not have sexes, just so-called mating types. A new study shows that there are great similarities between the parts of DNA that determine the sex of plants and animals and the parts of DNA that determine mating types in certain fungi. This makes fungi interesting as new model organisms in studies of the evolutionary development of sex chromosomes.

sex chrosomes

In the plant and animal kingdoms there are individuals of different sexes, that is, bearers of either many tiny sex cells (males) or a few large ones (females). In the third eukaryote kingdom (organisms with DNA gathered in the cell nucleus), the fungi kingdom, there are no sexes but rather a simpler and more primitive system of different so-called mating types. These are distinguished by different variants of a few specific genes.

There are many ways to determine sex. In humans it is done by sex chromosomes. It is thought that this sex difference arose in the plant and animal kingdom from the simpler system of mating types and that this happened several times independently of each other throughout evolution. The change is believed to have happened with the inhibition of a step in the copying process in DNA, which led to two separate chromosomes. These then developed further over a long period of time.

"In humans, sex chromosomes are believed to have developed over the last 300 million years from a common 'proto-sex chromosome,'" says Hanna Johannesson, who directed the study.

The new study shows for the first time that even though fungi do not have sexes, there are many similarities between the parts of the genome that determine sex in plants and animals and the parts of the genome that control mating types in certain fungi. The research group specifically studied a spore sac fungus (Neurospora tetrasperma) and can show that the similarities are great, regarding both present-day structure and the way in which it arose.

"It's hard to study the evolution of sex chromosomes, partly because so many different and important sex-specific characters are tied to them. But much of this can be avoided if we use simpler systems, like fungi, as models."