Journal Review

Will genome map lead to bug’s Achilles’ heel?

Cracking code may open up future clinical benefits

Woodford N, Livermore DM. Reflections and Reactions: Can we beat MRSA now that we know its genome sequence? Lancet 2001; 1:9-10.

Methicillin-resistant Staphylococcus aureus (MRSA) has long been the Tyrannosaurus Rex of nosocomial pathogens, but newly discovered genetic secrets could one day spell its extinction.

"Knowing the genome sequence does not beat MRSA, but it gives us — for the first time — a precise coastal chart from which to plan an invasion," concludes a recently published report by scientists at the Antibiotic Resistance Monitoring and Reference Laboratory in London.

The optimism comes after other researchers cracked the bug’s code and published the genome sequences for two strains of methicillin-resistant MRSA: Mu50 and N315.1 Of particular importance, Mu50 is the "prototype" vancomycin-intermediate S. aureus (VISA) first discovered in Japan. But what is the clinical significance of this information?

"What difference will the sequence make?" the researchers concede. "To the clinician who wants to know, Can I send MRSA isolates for sequencing, and will this knowledge help to cure my patients?’ Both answers are No.’"

Situation could change suddenly

However, automated sequencing and DNA chip technologies are developing at such a pace that the situation could change. First, based on the sequences now available, DNA chips can be constructed to represent the entire S aureus genome and used to study gene expression in different strains, and under different growth conditions. Comparison with sequences for other organisms will open new insights into pathogenicity.

The genomes of N315 and Mu50 revealed almost all of the known staphylococcal virulence factors, plus 70 new candidates. Those comparative data may assist the design of tests for VISA, the much-feared superbug that cannot be detected by routine disc diffusion tests.

"As more genome sequences are available, comparative genomics will allow structured approaches to fundamental questions, such as why some MRSA strains are better able to colonize, spread, and infect than others," the authors note.

". . . It is not difficult to imagine a time a few years from now when bedside molecular tests will establish not only whether a patient is colonized or infected with an MRSA, but also what antibiotic resistances the strain has and whether it is likely to spread. Such information will benefit therapeutic choice and will guide risk management by infection-control teams," they add.

Other benefits could include the development of new anti-staphylococcal agents and a better understanding of transfer of genetic information between microorganisms.

Reference

1. Kuroda M, Ohta T, Uchiyama I, et al. Whole genome sequencing of methicillin-resistant Staphylococcus aureus. Lancet 2001; 357:1,225-1,240.