April 19, 2001 -- When introduced in the 1930s, the first antibiotics were nothing short of miraculous. Sulfa and penicillin cured diseases that routinely killed thousands. But reckless use has weakened our strongest antibiotics, leaving us at the mercy of bugs that seem to be getting 'smarter.' Fortunately, scientists have begun to learn just how these bacteria outwit us, and this powerful information should lead to new, more powerful drugs.
To understand how bacteria become resistant to antibiotics, Keiichi Hiramatsu and colleagues in the department of bacteriology at Tokyo's Juntendo University looked very closely at strains of a very dangerous, very common bug called Staphylococcus aureus, or 'staph.'
"S. aureus is a ubiquitous pathogen in hospitals and in the community," Hiramatsu tells WebMD. "It produces an array of toxins that cause food poisoning and life-threatening syndromes." Not only does it cause toxic shock syndrome and a host of other ills, what's really scary is that some S. aureus strains are nearly untreatable. Nothing kills it.
"MRSA, or methicillin-resistant S. aureus, is a multidrug-resistant strain that responds to practically no antibiotics developed so far," adds Hiramatsu. And a strain called VRSA, or vancomycin-resistant S. aureus, has rendered vancomycin -- a 'last-resort antibiotic' -- useless.
Obviously, new drugs are needed, and soon.
"To understand the mechanism of developing antibiotic resistance, we had to unravel the entire genome of S. aureus," says Hiramatsu. To do so, he and his team analyzed and compared the complete genetic code of an MRSA and a VRSA strain.
"The study revealed S. aureus' extreme flexibility in adapting to antibiotics and causing infection," he tells WebMD. "We found multiple genetic elements [for] antibiotic resistance and toxin genes scattered throughout the genome of MRSA, suggesting that they are acquired from other bacterial species."
What's more, he says, "S. aureus generates new toxins and new [infectious] surface proteins by duplicating genes after it has acquired the originals."
In a nutshell, S. aureus hijacks genes from stronger bugs, incorporates them into its own genetic material. This enables the bacteria "to produce infinite combinations of toxins and ... establish infection in practically all human beings, regardless of ethnic or genetic backgrounds," says Hiramatsu.
Staph is not always a menace. In fact, it is a harmless resident in the nose of many healthy adults and most children. But as part of our "normal bacterial flora, it has been exposed to numerous kinds of antibiotics" over the years, says Hiramatsu. As each round kills off weak bugs, S. aureus' ability to usurp genes has allowed the survivors to grow even stronger. And when these superbugs pass from one person to another, it's trouble.
With this better understanding of S. aureus' genetic code and how the bug functions, "we can develop novel therapeutic agents and effective vaccines to prevent infection," says Hiramatsu.
But that will still take time, says Christopher Walsh, PhD, who reviewed the paper for WebMD.
"This [information] probably reduces the prospects from 2,500 genes -- which are the targets of drug development -- to two or three dozen," he says. That is quite a search, but "it's a hundredfold reduction in complexity."
Hiramatsu's team has "given us the complete catalog and told us what pages are most important to look at," says Walsh, who is the Hamilton Kuhn Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School in Boston. "People who make new drugs for a living will know to study those pages first, and presumably get there 100 times faster."
"S. aureus is a tough enemy and the genetic analysis fully confirms that," says Hiramatsu. "It would be impossible for us to destroy it, no matter what new drugs come in the future." If there's one message to take from this study, then, it's that "antibiotics should be used cautiously," he says.