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Genentech drug adds antibiotics to proteins to fight hidden bacteria

Technique helps antibiotic kill bacteria hidden in cells

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Scientists at Genentech have armed the body’s immune system warriors with antibiotics — which means that bacteria that hide from drugs inside cells are now targets.

In a study published today in Nature, scientists linked an antibody with a derivative of a group of antibiotics called rifamycin. This resulting drug proved to be a powerful new treatment against Staphylococcus aureus; it actually helped mice clear staph infections at a stage when conventional antibiotics normally stop being effective. But that's only part of the reason why researchers are excited about the technique. What's truly different here is that — unlike the related antibiotic rifampicin — the linked antibody-antibiotic unit can kill Staphylococcus bacteria inside cells. This means that it might one day be possible to use this technique to treat people with life-threatening antibiotic-resistant infections.

Bacteria that hide from drugs inside cells are targets

Staphylococcus aureus is a very common bacterium; about 30 percent of people carry it around in their noses. Most of the time that isn't a problem, but sometimes the bacterium causes serious, repeated infections that can be fatal. And to make matters worse, certain strains have become resistant to common antibiotics. As a result, one type of resistant staph bacteria — called MRSA — causes over 80,000 infections and 11,285 deaths occur every year. That's why researchers want to find ways to kill the pathogen when it's located inside cells, a hideout where antibiotics typically used against staph infections aren't as effective.

"Staph can hide inside blood cells for a couple of hours or days, and then they burst open and come out and they infect other cells," says Sanjeev Mariathasan, a biologist Genentech, the biotech company behind the study. That's a big problem because drugs that are normally used against staph infections can take over four hours to work — far longer than it takes for Staph bacteria to move into new cells, he says. "So we asked the question: 'Can we tag the bacteria with antibodies armed with really potent antibiotics and kill these pathogens inside the cell?'"

Mice recovered much sooner

That's exactly what the researchers did in this study — and it seems to work, at least in mice. Animals who received the treatment were able to recover from staph infections much sooner and with fewer negative health effects than they would have otherwise, Mariathasan says.

Antibodies are made, of course, by the immune system — but for the last several decades, biotechnology companies have made them as well. Genentech manufactured antibodies based on those the immune system makes to combat staph infections. Then, the researchers attached the antibiotics to the antibody by using amino acids as glue. When combined, the drug becomes far better at specifically targeting staph at specifically targeting Staph bacteria compared with conventional antibiotics.

"The researchers showed that the drug was effective against this strain; it worked the way it was designed to," says Gerald Pier, a microbiologist at Harvard University who also acts as a consultant for Visterra, a biotechnology company that's working on a similar technique. Now, the researchers have to show that it works against multiple strains of bacteria as well, he says.

The drug is definitely in its infancy, but it holds a lot of promise. Scientists haven't been able to conclusively say whether Staph bacteria hidden in cells are responsible for repeated infections, but if that's the case, then this treatment could put a stop to that by clearing the body of bacterial reservoirs. Because the drug acts inside cells, it's possible that this treatment might one day help people avoid repeated infections, Mariathasan says.

This might help people avoid repeated infections

The technique might also prove to be less harsh on the body than common staph treatments. Because the antibiotic is only active inside infected cells, it won’t wipe out the other bacteria — beneficial bacteria — with drugs distributed more broadly in the body. That means that people might end up being less vulnerable to other illnesses than they normally would following the treatment.

The study has some limitations, however. The experiment was only done in mice and in vitro cells — neither of which are good indicators of a drug's effect on humans. Mariathasan declined to tell The Verge when those trials might begin, but he says that Genentech is "obviously interested in whether this translates into human results." In addition, the drug is very specific, and so if it does make it to humans, doctors will probably only be able to give it to patients with a firm diagnosis. In some parts of the world, that kind of diagnosis isn’t possible.

Still, the act of combining two different weapons — antibodies and antibiotics — to fight off infections is an intriguing idea. Today’s study suggests the technique is ripe for exploration.

Correction: A previous version of this article stated that the antibody was linked to the antibiotic vancomycin. That is incorrect. The antibody was actually linked to a derivative of a group of antibiotics called rifamycin. The drug was therefore compared to the related antibiotic rifampicin. We regret the error.