Amazing Bacteria Communication

[Skeptic Ginger]

Split from Medicine should be taught in high school

Blutoski posted some interesting stuff about bacteria:

... Try to visualize a graph representing the total quantity of living bacteria versus time. With exposure to antibiotic at t=0, there's 100% of the original population. As we move forward in time, the population will start to decline, but slowly at first.

The shape is called a reverse s curve, or playground-slide-shape.

The rate of dieoff increases, then levels off. So: after a half course, there is, say 99% of the original starting population, versus .0001% after a full course.

Now, also consider that the ability for resistance to either be propagated by plasmid or formed by ne novo mutation is proportional to the number of individual cells per body - in other words: density - (since they need to be near each other to transmit plasmids - the host environment is hostile to free-floating DNA), and to some extent, also the number of cell divisions (in bacteria, the majority of mutations or recombinations happen once per cycle).

So: the half-course reduced density and population by 99%. The full course by 99.9999%. The chance that the surviving flora will be resistant could be reduced by many orders of magnitude.

It's a sort of herd reverse-immunity for bacteria: keep the density low, and the resistance isn't "passed" as much. This is not a proportional thing: there's a density threshold beneath which plasmid distribution or de novo mutation or recombination to resistant strain simply becomes nonexistant. The course just has to pass this sweet spot.

analogy again with herd immunity: you don't need 100% inoculation to make a population 'safe,' and there's probably no difference between 100% and 90% inoculation. But suddenly around 89%, an infectious agent will run through a population like wildfire. Round numbers for illustration.

The other benefit is related to the likelihood of propagating the infectious cells to other hosts.

There was a discussion about hospitals earlier. Based on what has been successful in reducing MRSA &c, course length does not appear to be the problem. The problem is that so many infected people are concentrated in the complex, and secondly, that ventilation, equipment sterilization and general houskeeping have not been fully exploited as part of the solution.

The original mutations are probably millions of years old, but a patient drags the bacteria in, and sheds a few onto the pillow while sleeping. The housekeeper comes in and changes the pillow, but does a poor wipe-down with antiseptic. The MRSA sits on the pillow, or possibly even inside the pillow, slowly growing in colony size, and eventually is inhaled by a patient, who gets an overgrowth, sheds it on a neighbour, and the cycle continues.

So, the current best-practices include easy tips such as using disposeable cuffs, gowning more visitors, and so on.

Anyway, the point is that the half-course patient is shedding 10,000x more gribblies on the pillow for the next guy, and they're perhaps a million times more likely to have been dense enough to have shared a beta lactamase plasmid.

And while the post only briefly touched on the plasmids needing a particular density to propagate, that was the issue that caught my attention. (Plasmids are little vessels that carry genes from one organism to another.)

Anyway, it seemed there might be some implications regarding a NOVA - Science Now program that recently aired on PBS, "Bacteria Talk".

Bassler: What's become clear in the last decade is that all bacteria talk to each other. Bacteria are chattering like crazy. Once quorum sensing genes were found in bacteria that people think are important—like pathogens—more and more people started entering the field. Now hundreds and hundreds of labs work on quorum sensing.

We now realize that the way we all used to think of and study these bacteria—as these asocial, reclusive, shy organisms—is completely wrong. This isn't how they're living out in the wild. And so there's been this sort of paradigm shift. It turns out we just completely missed the boat, myself included, until about a decade ago. I think my lab played a big part in making the world see that bacteria have these complicated vocabularies that are made up of many different molecules, and that this is very much like how cells inside the human body interact.

Quorum sensing genes allowed the organisms to communicate with other bacteria. When the colony detects it is large, different processes are initiated. In the case of the weird bacteria studied by Dr Bassler, when they sensed a quorum, they glowed. That launched a whole new field looking for these communication molecules.

We want to understand cell-to-cell communication, and we know that the indicator of when the bacteria are talking is that they glow. So we try to make mutations so that the bacteria don't make light when they are together, or do make light when they are on their own. Then we can go back and figure out what's wrong with them.

And that's when they found out quorum sensing was a common trait among bacteria.

Bassler: The question is, can we control quorum sensing? Hopefully, the answer is yes. We understand that bacteria control virulence as a group, as a function of quorum sensing. We know that different species of bacteria can trick each other and garble up each other's languages. We humans are not so dumb, we should be able to do that, too. And so there is this tremendous move in the quorum-sensing field to try to develop a whole new kind of antibiotics based on anti-quorum sensing strategies.

And bacteria also do all kinds of good things for us—we use bacteria to make all kinds of human products. So we would also like to make molecules that enhance quorum sensing, so that we can exploit the good bacteria and get them to do things that we want them to do even better.

Q: Like?

Bassler: Like making insulin and other drugs that we mine from bacteria. Another idea is to try to control commensal bacteria—those 1010 bacteria that are in you, and on you, and all over you. They also have quorum sensing. We might be able to make them better at fending off predators or invaders. Maybe we can make pro-biotics that help you not get sick in the first place. There are all these ideas for manipulating quorum sensing that have very practical human consequences. It's an amazing dream.

It would also seem to have some implications about how single celled organisms might have come together into multicelled organisms. These chemicals are akin to hormones and maybe even suggest the potential precursors to neurotransmitters.

Hopefully blutoski will have time to tell us if the plasmids are affected by quorum chemical sensing or whether it is just increasing chance of plasmid gene transfer in concentrated bacteria colonies. And the other fascinating question I have is, are the bacteria directing which genes to send out in the plasmid vehicles? If blutoski doesn't have time, or someone else doesn't know, I'll try to look into it further.

 

[kellyb]

Here's another article on quorum sensing:

http://www.sciam.com/article.cfm?articleID=0001F2DF-27D8-1FFB-A7D883414B7F0000

As its moniker suggests, quorum sensing describes the ways in which bacteria determine how many of them there are in the vicinity. If enough are present (a quorum), they can get down to business or up to mischief. For instance, millions of bioluminescent bacteria might decide to emit light simultaneously so that their host, a squid, can glow--perhaps to distract predators and escape. Or salmonella bacteria might wait until their hordes have amassed before releasing a toxin to sicken their host; if the bacteria had acted as independent assassins rather than as an army, the immune system most likely would have wiped them out. Researchers have shown that bacteria also use quorum sensing to form the slimy biofilms that cover your teeth and eat through ship hulls and to regulate reproduction and the formation of spores.

Bassler came to work with Silverman in 1990, after finishing her doctorate at Johns Hopkins University. She decided to focus on another glowing marine bacterium, V. harveyi, to determine whether its signaling system was similar. She got to work making mutant bacteria--disabling a gene here, a gene there, to see if she could impair the one that triggered the bug to bioluminesce when it was in like company. "You turn off the lights in the room and just look for the ones that are dark when they should be bright or bright when they should be dark. It is genetics for morons," she quips. Bassler found the genes for V. harveyi's autoinducer and its receptor.

She also discovered something surprising. If she knocked out those two genes and put the altered V. harveyi in mixed company--that is, around masses of different species of bacteria--it glowed. "So I knew there was a second system," Bassler remarks. Bacteria "don't have enough room in their genome to be stupid, so there had to be a separate purpose for this system." The foreign bacteria were emitting something that V. harveyi responded to. Bassler called that something autoinducer two

Some scientists are also concerned that aspects of quorum sensing--but not Bassler's findings--have been slightly overinterpreted. "Do bacteria want to communicate with each other, or is it just by accident?" asks Stephen C. Winans, a microbiologist at Cornell University. "This idea has taken hold that these bacteria want to communicate with each other. It may be just too good to be true."