My name is Michele LeRoux

and I did my graduate work at the University of Washington in Seattle.

And I'm going to tell you today about work I did in graduate school

studying how bacteria interact with one another

and how they survive out in the environment

and in our bodies.

So, I'm going to start out by telling you that

I really love yogurt.

It's one of my favorite foods,

I eat it almost every day,

I even make my own yogurt now,

but early on in graduate school

I was looking at one of those little yogurt containers

where it says, "Contains live and active cultures,"

and I wondered whether that was really true.

Would I really see bacteria in there?

So, I took a little bit of yogurt

and I put it on a slide

and I went and looked at it under the microscope.

And this is the picture I took.

Look at all those bacteria

-- there's long rods, there's short rods,

there's these little coccoid bacteria

that are forming these chains --

and actually different types of yogurt

had slightly different bacterial groups in them

that gave them different tastes,

so this was really my first exciting glimpse

into this invisible world of bacteria

that are all around us.

They live in these communities

and they make delicious things for us to eat.

So this got me really excited about the idea of

studying how bacteria live in these communities together.

So, of course, bacteria are not just in our yogurt;

they're out in the environment,

everywhere you look, basically,

associated with plants,

in the soil, in the water,

there's bacteria in the ocean.

Every teaspoon of sea water

has about five million bacteria in it,

so think about that the next time you

accidentally swallow a little ocean water.

That's a lot of bacteria that you've just taken into your body.

And then, as I mentioned before,

there's bacteria in our foods.

Cheese is another type of food

that we require bacteria to make for us,

and of course there's bacteria in our bodies,

in our guts there's billions of bacteria,

there's bacteria in our mouths and our skin,

and a lot of them perform

really important functions for us.

They help us digest our food

and they help our immune systems work properly as well.

But of course, bacteria can also cause

really, really devastating infections,

and that's actually usually what we've been studying them for

in the past.

So, the organism that I'm going to tell you about today

is this organism called Pseudomonas aeruginosa.

And this is an organism that's

actually mostly found out in the environment.

It lives in the soil, it lives in the water,

and we come into contact with it all the time.

It lives all over the place.

So, mostly, it doesn't really cause us a lot of problems...

but occasionally Pseudomonas can get into

a particular human environment

and it can really wreak havoc.

So, this is a little bit like a termite.

You know, a termite,

mostly, it lives out in nature,

it can build some really cool mounds,

it will digest cellulose in wood

and it plays a really important role in the ecosystem,

but if a termite gets into someone's home,

into the wooden framework,

and starts chewing up that wood,

it can be really hard to get rid of

and it can bring the house down.

So, it's the same with Pseudomonas.

You know, mostly we don't worry about it,

but if Pseudomonas gets into the wrong human environment,

it can be really devastating.

So, what environments are those?

A lot of might have loved ones, family members,

that are in nursing homes

or are confined to wheelchairs,

and people like this are often

prone to getting bedsores or chronic wounds.

These are also common in people with type II diabetes.

And these are wounds that just cannot heal;

they just stay open wounds for,

sometimes, years.

And they can get infected with bacteria.

So, especially if Pseudomonas gets in there,

it can be really, really bad for these people.

It can get deep into the tissues

and it can be impossible to eradicate

and sometimes leads to amputations or even death.

And we don't quite understand

why it's so difficult to treat Pseudomonas infections

when they get into these chronic wound environments.

Another environment that Pseudomonas really thrives in

are the lungs of patients with the genetic disease

cystic fibrosis.

So, these people have

a mutation that causes them to have

really thick mucus in their lungs,

and this makes an ideal environment for this bacterium.

In fact, 80% or more of people with cystic fibrosis

will acquire Pseudomonas at some point in their lifetimes,

and once they do it's

impossible to eradicate it most of the time.

And it will go on to lead to the

decline of their lung function and ultimately their deaths.

So we really, really need to understand better

how Pseudomonas is causing these problems

and how we can treat these infections with Pseudomonas.

So, what I decided to do was

to kind of step back from thinking about Pseudomonas

interacting with humans, directly,

and think more about,

what does Pseudomonas need to survive?

What is motivating a lot of its behavior?

How has it evolved over the years?

So what I decided to do was

think about putting myself in the shoes of this bacterium...

well, of course, not exactly in its shoes,

because it's a bacterium, it's a single-cell organism,

it doesn't wear shoes...

but thinking about what it needs to survive.

So, Pseudomonas needs, just like us,

food to eat.

It needs a place to live, it needs a home.

And it will fight to the death

to be able to make sure

that it maintains these resources.

And, actually, usually what it's fighting

are other bacteria that it's competing with

for its food and its home.

So this is where it's really helpful to think about

how long bacteria have been around

and what's really been driving their evolution.

So, the Earth first evolved

around four and a half, give or take, billion years ago,

and not too long after that, in evolutionary terms,

there's evidence of the first bacterial fossils.

Sometime later,

we have evidence of the first bacterial ecosystem

-- so, these are where groups of bacteria live together

and interact with one another,

so this is where bacterial interactions

would have first started evolving.

Now, eukaryotes didn't show up on the scene

until much, much later,

and of course humans have really only been around

for the blink of an eye in terms of evolutionary time.

So, this green bar

represents the amount of time that bacteria

have been interacting with other bacteria.

That green bar, that you can barely almost see over there,

that I'm showing you down here,

is how long that bacteria have had

to interact with humans.

So, it's a much, much smaller amount of time,

and yet that's what we usually end up studying in the lab.

So I thought, well,

there's probably a lot to be learned about bacterial behavior

if we focus a little bit more on

bacterial interactions with one another,

and that might even inform

how we think about their interactions with humans.

So, what I decided to do was

to start by focusing on one particular bacterial weapon

that it uses to compete with other organisms,

and that is this secretion system

called the type six secretion system.

You can think of it as a syringe

that injects toxins from one cell into another,

and this pathway was actually

not discovered too long ago,

and the lab that I did my graduate work in, the Mougous lab,

were one of the first to show that

this pathway actually

injects toxins from bacteria into other bacteria.

So this is kind of what this might look like.

If you have this green cell,

let's say this is the Pseudomonas cell,

it has these little red dots that are representing toxins,

it will literally inject them into the cell next to it,

which will cause...

these toxins will cause this other cell to die.

And if we zoom in on this a little bit,

you can see this syringe, here,

I'm depicting as kind of a tube,

but it's actually a molecular machine

made up of a bunch of different proteins

that are able to push proteins

-- toxins --

from one cell into another cell.

And these toxins have all kinds of different functions,

we're still discovering new ones all the time,

but, for example,

they might degrade the cell wall of the recipient bacterium,

which would cause it to burst,

the might attack the membrane of the cell,

and some of them even go after molecules

that are required for survival,

such as RNA or DNA or energy molecules.

And all of these things will cause the cell to die.

So, the next thing I want to do is show you

what type six looks like in action.

But before I can do that,

I have to explain to you what to look for.

So, how do we watch cells dying in the lab?

Well, what I like to do is

I have cells that are expressing

a colored protein, such as green fluorescent protein

-- they're making a lot of it,

so they appear green when you look at them --

but if that cell were to get

a rupture in its membrane or its cell wall,

what would happen is that the green protein

will flood out of the cell,

and then after just a second or two

that cell will appear dark.

So you're literally just going to see a green cell disappear.

But really what's happening is that cell is bursting open

and spewing out its guts into the surrounding area.

And so just keep that in mind:

when you see a cell go dark, really it's exploding in a...

actually a pretty violent way.

So, let me show you what I'm talking about.

So, here we have Pseudomonas aeruginosa

and it's labeled in a red color,

and we have a competitor organism

that's labeled green.

So, you're going to be looking for these green cells

to just disappear.

So, to make it a little bit easier to identify those,

I had the software that I use to analyze this data

outline them in a white outline

so you can find them more easily with your eye.

So, just one note about this competitor organism:

this is an organism that's called

Burkholderia thailandensis.

This is another bacterium that lives in the soil

that would potentially interact with Pseudomonas

in the environment.

You don't have to remember the name