Human World

Jorge Galan reveals Salmonella’s stealth, and also its Achilles heel

Yale researcher Jorge Galan has spent over two decades trying to figure out how Salmonella – the bacteria the causes food poisoning – attacks our bodies, and makes us sick. In a paper that appears today in the journal Science, Dr. Galan reveals a discovery that could lead to an antidote for salmonella poisoning, and even the creation of next-gen antibiotics. His team has uncovered, he says, the mechanism by which salmonella hijacks our intestines, cell by cell. He told EarthSky:

It needs to comandeer the functions of those [intestinal cells], it needs to get the cells to do some work for Salmonella, if you will. In order to do that, it has this remarkable device which, for all intents and purposes, is like a nano-syringe.

Image Credit: Jorge Galan

A nano-syringe is a syringe of a very tiny size. In a matter of seconds, Dr. Galan says, a Salmonella bacteria can attach to a healthy intestinal cell, and launch an attack by injecting a bunch of proteins with its microscopic syringe.

It can inject these proteins, that’s remarkable enough, but it has to do this in a very, very precise order. So, imagine that the syringe has to inject protein A, B, C, D. The question is, how do you establish that order?

He says the first protein that marches out of a Salmonella “syringe” helps the bacteria puncture the intestinal cell to which its attached. That allows the other proteins to gain entry, and hijack the healthy cell. When Salmonella bacteria do this in great numbers, food poisoning occurs. But Dr. Galan’s focus is on the little picture, as opposed to the big.

His major finding is that individual Salmonella bacteria are a little like delivery trucks. In a delivery truck, packages are often placed according to when and where they need to be delivered. For speed, and for accessibility by the driver, right?

Same thing with the inside of a Salmonella cell. Salmonella’s proteins – the ones it uses to hijack our cells – are organized according to where and when they need to be delivered. It’s this ordered, organized protein delivery system that explains the bacteria’s raging success inside our guts.

But this protein delivery system, or “platform” as Dr. Galan calls it, is also a kind of Achilles heel, it provides drug researchers with a target. If a drug can simply mess with Salmonella’s ability to order its proteins, that drug can stop Salmonella in its tracks.

We scientists, when we describe the mechanism of how things work, we are not directly making a drug, but we provide the basis so that other people that having a goal of making a goal of an anti-Salmonella drug, an anti-infectanct, and anti-microbial, they can design the drug around the concept of inhibiting the mechanism that we have described.

Image Credit: Thomas Marlovits

That’s critical, he said, because about half a million people die each year from Salmonella (and salmonella-induced typhoid fever) across the world. Salmonella strains outside of the U.S. can be quite deadly, Galan says. Children are particularly susceptible to Salmonella exposure in the developing world. That’s true for young children in the developed world, too. In the U.S., Salmonella sickens at least 40,000 people annually, and kills about 400 people, according to the Centers for Disease Control.

But Galan is hoping to curb more than just Salmonella outbreaks. He indicates that lots of bacteria are thought to organize proteins like Salmonella does. (Bubonic plague and whooping cough are particularly nasty examples). That being the case, Galan’s research paves the way not just for an anti-Salmonella agent, but a whole range of antibiotics that could scramble the “brains” of an entire class of infections – that is, interfere with their ability to fully organize their attack. Galan explained:

These drugs would not kill the bacteria, but would simple cripple their ability to cause disease. …For reasons that are a little technical, the chances of developing resistance to those drugs, it tends to be much much less than the chances of developing resistance to drugs that kill bacteria. So future drugs are going to center more around this concept, trying to cripple mechanisms that we know are essential for the bacteria to cause the disease, rather than drugs that outright kill microbes.

So – after two decades of research – Yale researcher Jorge Galan has revealed a discovery that could lead to an antidote for salmonella poisoning. Fingers crossed that it will lead to the creation of next-gen antibiotics. Next time you eat a burrito that’s got you doubling over the next day, it might make you feel better just to keep Dr. Galan in your thoughts.

February 3, 2011
Human World

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