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Genomes of two drug-resistant Staphylococcus aureus strains are sequenced
  
By Bijal P. Trivedi

Japanese scientists have sequenced two strains of the bacterium Staphylococcus aureus, which have acquired resistance to virtually every available antibiotic. Researchers hope that comparing the sequences will lend insight into the evolution of drug resistance and lead to the identification of genes that can be targeted by a new generation of antibiotics.

The scientists sequenced a meticillin-resistant strain of S. aureus (MRSA N315) that was isolated in 1982. These bacteria are resistant to most penicillins, which kill by preventing the bacterium from building its cell wall. The only weapon against meticillin-resistant bacteria is vancomycin. But, in 1997, scientists isolated a strain of vancomycin-resistant S. aureus (VRSA). The Japanese team, led by Makoto Kuroda, of Juntendo University in Tokyo, Japan, also sequenced the vancomycin-resistant strain, Mu50. Descriptions of both genome sequences appear in the current issue of The Lancet.

The greatest concern has been that once resistance has evolved, it will spread rapidly among diverse families of bacteria. From studying the genome sequences of the two related S. aureus strains, Japanese scientists found that antibiotic resistance genes are carried on small circles of DNA called plasmids, which are distinct from the bacterium's main chromosome. Resistance genes are also carried on mobile sections of DNA that can 'jump' from one location of the chromosome to another.

Kuroda's team discovered a 'resistance island' called SCCmec—a cluster of genes that encodes resistance factors to more than five families of antibiotics. The fast-paced lives of bacteria and the mobility of plasmids and 'jumping' genetic elements promote the spread of resistance through the bacterial community.

Resistance genes are not the only problem. S. aureus produces a huge variety of toxins. Kuroda's study identifies 70 genes that could potentially contribute to the bacterium's virulence. In addition, the researchers identified three new types of 'pathogenicity islands'—gene clusters associated with different types of toxins.

One particularly surprising feature of the sequenced genomes is that S. aureus carries a hodge-podge of genes acquired from a myriad of organisms, ranging from other Staphylococcus bacteria, to more distant bacterial relatives, to humans. The Japanese scientists remark that finding such a diverse mixture of genes is unexpected because S. aureus was not thought as capable of acquiring foreign DNA as other bacteria.

S. aureus is a very successful pathogen. It infects about one-third of the world's population, living a benign lifestyle in the nasal membranes and skin. It is a major cause of infection in and out of the hospital. The bacterium is responsible for a broad spectrum of infections, ranging from mild skin infections and food poisoning to life threatening conditions like sepsis, pneumonia, and infectious endocarditis.

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Kuroda, M. et al. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357, 1225-1239 (April 21, 2001).
 

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