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Superbug dissected

MRSA strain uses a deadly protein to attack the immune system.

Some antibiotic-resistant bacteria are nastier than others. Credit: BIOMEDICAL IMAGING UNIT, SOUTHAMPTON GENERAL HOSPITAL / SCIENCE PHOTO LIBRARY

The nastiest strains of Staphyloccocus aureusdeliver molecular bombs that kill immune cells, researchers have found. The protein bombs are one of the features that distinguish the more vicious strains of drug-resistant S. aureus that are now tearing through communities from those that have plagued hospitals for decades.

The proteins ? called phenol-soluble modulins, or PSMs ? are just one of many tricks up the sleeve of drug-resistant S. aureus. Targeting the proteins with an anti-serum at the same time as bashing the microbes with antibiotics that still have some effect, such as vancomycin, might help to beat back the tide of rising infections.

S. aureus has a nasty habit of being resistant to the drugs used to treat it, often with deadly results. Methicillin resistant S. aureus(MRSA), which is also resistant to many other commonly-used drugs, causes more than 18,000 deaths in the United States every year ? eclipsing the approximately 16,000 deaths from HIV/AIDS in 2005.1 And infections are also on the rise: in 1974, MRSA was responsible for 2% of Staphylococcus infections, but by 2003 that proportion had risen to 64%. Symptoms range from pimples to puss-oozing boils to pneumonia.

There are different types of MRSA. Community-associated MRSA is resistant to fewer antibiotics than hospital strains are, but is more ferocious, able to fell people within days.

First defence

Michael Otto, a microbiologist at the National Institute for Allergy and Infectious Disease in Hamilton, Montana, and his colleagues were looking at the ways that MRSA can be so nasty when they discovered the PSMs: proteins 20?40 amino acids long and related to PSMs found in a species of Staph that coats our skin

To determine how these molecules inflict their damage, Otto?s team made several of them in the lab and rained them onto a type of human immune cell called a neutrophil. These cells are the body?s first line of defence against Staphylococcus and they are key to battling infection. Within minutes these immune cells started to flatten (a sign of stress), and after an hour many were destroyed.

?This is how we think S. aureusgets rid of its main enemies,? says Otto.

Otto?s team examined a collection of hospital and community strains that had been isolated from patients, and found that several of the community strains produce lots of PSMs, while most hospital varieties made none. They concluded that this might be one of the reasons that community-based MRSA is so bad.

A second experiment confirmed this idea. Removing the genes encoding for PSMs lessened the community-based bacteria?s ability to kill lab mice, and left smaller abscesses on the skin of infected mice than usual, the group reports in Nature Medicine2.

Multi-pronged attack

Though PSMs seem to be important in understanding community-associated strains, they are one piece of a larger puzzle, says Henry Chambers, a microbiologist and physician at the University of California in San Francisco. ?It is unlikely and in fact na£ve to suspect that there's a one size fits all virulence determinant in Staphylococcus,because they have so many,? he says.

Researchers have identified other proteins and toxins produced by community-based strains that boost their infectivity (see Research highlights nastier form of MRSA).

Otto's team is now making PSM antisera to test in mice infected with community-associated MRSA.

References

  1. Klevens, R. M. et al.JAMA 298, 1763?1771 (2007)

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  2. Wang, R. et al. Nature Med. doi:10.1038/nm1656 (2007).

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Callaway, E. Superbug dissected. Nature (2007). https://doi.org/10.1038/news.2007.235

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