London--Talk about a transformation worthy of Superman. In the St. George's Hospital here, a mild-mannered bacterium most people carry without harming their health turned into a dangerous variant that not only resisted an antibiotic--it thrived on the drug, says a report in Saturday's issue of The Lancet.
The story begins earlier this year, when two patients--one who had a cancerous prostate removed and another who was being treated for a punctured esophagus--came down with severe bacterial infections in the hospital. One of the culprits, a common bacterium called Enterococcus faecalis, was sensitive to the antibiotic vancomycin, so the patients received this or a similar drug.
Soon, however, it became clear that the antibiotics had failed to wipe out the bug. In fact, not only were the surviving bacteria isolated after more than a week of treatment resistant to vancomycin, they even appeared to depend on the antibiotic for their own survival. "This is the first instance of isolating [the drug-dependent enterocci] in sick patients, where [the bugs] were almost certainly contributing to the infection," says the report's lead author, Ian Eltringham, a clinical microbiologist at St. George's Hospital Medical School. While finding organisms resistant to antibiotics is an increasing problem, antibiotic-dependent bugs are "extremely rare," Eltringham says.
The medical sleuths next wanted to know whether the antibiotic-dependent bacteria had mutated from the original form or were an entirely separate population. To do this, the Public Health Laboratory Service in Colindale, England, compared DNA strands using gel electrophoresis from each form of E. faecalis. The strands were identical, Eltringham says, suggesting the drug-dependent form had evolved from the other.
Eltringham proposes the following scenario for this breakneck capacity to evolve. The organism develops resistance to vancomycin by acquiring or activating an extra set of genes coding for enzymes that synthesize its cell wall. This machinery bypasses the normal synthesis pathway--vancomycin's target. The primary set of genes become inactivated, perhaps through mutation, leaving only the alternate pathway operating. Because the antibiotic-dependent variant disappeared after the treatment was stopped, Eltringham says, it seems that vancomycin induces the synthesis of these alternate enzymes. Without the antibiotic, the bacteria are unable to build a cell wall. This explanation "is perfectly plausible," says Mike Marriott, a microbial biochemist at Glaxo-Wellcome in Verona, Italy.
The two patients eventually recovered. However, vancomycin is becoming a widely used weapon against other drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus. Vancomycin-dependent E. faecalis could lurk in the shadows of other infections and become a dangerous surprise in severely ill patients. Thus, the report's authors ask, "Have we at last witnessed the emergence of a true superbug?" Stay tuned.