The killer hidden in plain sight

Scripps Research scientist Dr. Marta Perego

The phrase "antibiotic resistance" has become so common it rolls off the tongue, but what it actually means has been lost for most Americans.

What it means is that while heart surgery and hip replacement have become increasingly effective, hospital visits have become more and more dangerous as patients are exposed to troves of bacteria and as the drugs to fight them become less effective.

"Until a few years ago, we had one or two antibiotics that worked for all bacteria, but now there's so much more resistance and there's nothing new coming up," said Dr. Marta Perego, a Scripps Research scientist who specializes in bacteriology. "There's nothing in the pipeline. Most big pharmaceutical companies have dropped bacteria research."

Now, with antibiotic resistance high, it would take specialized drugs to cure bacterial infections. The problem is that treatment would only last about a week – not nearly enough time to win back the investment that drug companies would have to make in research. The financial pay off just doesn't calculate, especially when you consider that countering chronic conditions such as rheumatoid arthritis requires ongoing treatment that brings ongoing profits.

Dr. Perego laments what she calls a disconnect between the large number of deaths bacteria causes and the low levels of funding dedicated to understanding and fighting them.

"Despite the more than 90,000 deaths a year caused by bacterial infections in the U.S., public funding for basic research on microorganisms has been severely decimated in the last decade and amounts to probably one-one hundredth of the funding that is awarded to study diseases with less impact on mortality rates but supported by strong lobbying groups", she said.

At Scripps Research, where scientific and medical value rather than profits drive research, Dr. Perego studies a class of bacteria that are responsible for thousands of deaths each year, but are often overlooked by the scientific and medical community. By learning how these organisms live in their native habitats, and how and why they escape, she hopes to find ripe targets for new drugs that would make hospital visits safer for everyone.

Her particular focus is an organism called Enterococcus faecalis, which normally grows in the human intestine, but can escape and enter other parts of the body with dramatic health effects. It was the first kind of bacteria found to be resistant to vancomycin, the last antibiotic resort for curing bacterial infections, and in the last decade it has emerged as the third leading cause of healthcare-associated infections in the US.

Dr. Perego's lab investigates how Enterococcus faecalis survives in the intestine and how it escapes. The idea is that these studies could help identify critical pathways and proteins that could be targeted with antimicrobial drugs.

"What makes Enterococcus able to leave the intestine? Why does it leave? What makes it a pathogen?" Dr. Perego asks.

Bacteria have an innate ability to sense their environments. They can tell if they're in a warm or cold spot, they can determine whether there are nutrients available. They can even tell whether there are antimicrobial substances nearby.

Dr. Perego is studying the proteins that allow bacteria to sense these things, with the hope that she'll uncover clues to how to counter the organisms.

"If you do not know the subject which you want to fight, you're not going to be able to fight it," she said.