Resistant strains of Staphylococcus aureus, which are also called "hospital staph" because of their prevalence in hospitals, constitute 34 percent of the clinical isolates in the United States, more than 60 percent in Japan, Singapore and Taiwan, and more than 50 percent in Italy and Portugal. And the emergence of strains of Staphylococcus that are resistant to vancomycin -- the antibiotic of last resort -- makes public health concerns about drug- resistant strains of the bacterium even more urgent.

In an article published online on October 21, 2002, in the journal Nature Structural Biology, Daniel Lim and Natalie Strynadka, who is a Howard Hughes Medical Institute international research scholar, reported structural studies of the enzyme known as penicillin-binding protein 2A (PBP2a). Lim and Strynadka are at the University of British Columbia.

Before the advent of drug-resistant strains of Staphylococcus aureus, staph infections were treated using beta-lactam antibiotics such as methicillin, which block the bacterial enzyme PBP. This enzyme -- called a transpeptidase -- normally catalyzes the cross-linking of structural molecules in the bacterial cell wall. Blocking PBP with methicillin weakens the cell wall, which ultimately bursts, killing the bacterium.

However, a methicillin-resistant strain of the bacteria has evolved that has acquired the gene for a new version of PBP -- PBP2a --from another bacterium. The challenge, as well as the opportunity, said Strynadka, is to understand why PBP2a is resistant to beta-lactam antibiotics.

"What is very attractive from a therapeutic point of view is that PBP2a constitutes a single target, in terms of developing new antibiotics that can overcom
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
21-Oct-2002