Horizontal Gene Transfer: Plasmids

Peter Eisler has a somewhat scary article on the development of drug resistance in bacteria at the University of Virginia Medical Center. The bacteria were resistant to all of their antibiotics. Everything. And the bacteria were able to pass the genes that gave them their resistance to other bacteria: not just to their offspring, but horizontally to other species of bacteria by exchanging bits of DNA called plasmids.

One bacteria cell passes a piece of DNA (called a plasmid) to another. From USA Today — Image links to more complete information.

When genes are passed on from parent to offspring, or even from one microbe to another by cell splitting, it’s called vertical gene transfer. Horizontal transfer, on the other hand, involves different individual organisms passing genes from one to the other. It would be as if two people could exchange genes by shaking hands.

When the doctors began analyzing the bacteria in their first patient, who’d transferred from a hospital in Pennsylvania, they found not one, but two different strains of CRE bacteria. And as more patients turned up sick, lab tests showed that some carried yet another.

“We were really frustrated; we hadn’t seen anything like this in the literature,” says Costi Sifri, the hospital epidemiologist. “The fact that we had different bacteria told us these cases were not related, but the shoe leather epidemiology suggested to us that all these (infections) came from the same patient. … We realized we might be seeing a mobile genetic event.”

In other words, it looked like a single resistance gene was jumping among different bacteria from the Enterobacteriaceae family, creating new bugs before their eyes.

— Eisler 2012: Deadly ‘superbugs’ invade U.S. health care facilities in USA Today.

The really scary part:

There is little chance that an effective drug to kill [drug resistant] CRE bacteria will be produced in the coming years. Manufacturers have no new antibiotics in development that show promise, according to federal officials and industry experts, and there’s little financial incentive because the bacteria adapt quickly to resist new drugs.

Breeding Drug Resistant Bacteria at Farms

Modern commercial farming uses a lot of antibiotics, and, as a consequence, we’re beginning to see them breeding drug resistant bacteria (see here for exponential growth demo). Jeremy Laurance reports on one bug (MRSA ST398) now being found in milk.

Three classes of antibiotics rated as “critically important to human medicine” by the World Health Organisation – cephalosporins, fluoroquinolones and macrolides – have increased in use in the animal population by eightfold in the last decade.

The more antibiotics are used, the greater the likelihood that antibiotic-resistant bacteria, such as MRSA, will evolve.

The MRSA superbug can cause serious infections in humans which are difficult to treat, require stronger antibiotics, and take longer to resolve. Human cases of infection with the new strain have been found in Scotland and northern England

— Laurance (2012): New MRSA superbug strain found in UK milk supply in The Independent.

Note that consumers of milk don’t have to worry because the milk is pasteurized.

Anti-biotic Brass

Interesting research shows that brass and other copper metal alloy surfaces kill bacteria and degrade their DNA much better than stainless steel or plastic.

Plastic and stainless steel surfaces, which are now widely used in hospitals and public settings, allow bacteria to survive and spread when people touch them.

Even if the bacteria die, DNA that gives them resistance to antibiotics can survive and be passed on to other bacteria on these surfaces. Copper and brass, however, can kill the bacteria and also destroy this DNA.

— Grey (2012): Fit brass fixtures to cut superbugs, say scientists in The Telegraph.

Exponential Growth of Cells

Today I grew, and then killed off, a bunch of bacteria using the VAMP exponential growth model to talk about exponential and logarithmic functions in pre-Calculus. I also took the opportunity to use an exponential decay model to talk about the development of drug resistance in bacteria.

Two cells are reproducing (yellow) during a run of the exponential growth model.

Students had already worked on, and presented to each other, a few bacterial growth problems but the sound and the animation helped give a better conceptual understanding of what was going on.

After watching and listening to the simulation I asked, “What happens to the doubling time?” and one student answered, “It gets shorter,” which seems reasonable but is incorrect. I was able to explain that the doubling time stays the same even though the rate of reproduction (the number of new cells per second) increases rapidly.

Graph showing how the number of cells increases over time.
Switching from growth to decay (half-life of 50 sec).

Then I changed the model from growth to decay by changing the doubling time to a half-life. Essentially this changes the coefficient in the exponent of the growth equation from positive to negative. The growth rate’s doubling time was 100 seconds, but I used a half life of 50 seconds for decay to accelerate things a bit, but still show the persistence of the last of the bugs.

Exponential decrease in cell population/biomass.

The cells died really fast in the beginning, and while there was just one cell was left at the very end, it was pretty clear just how persistent that last cell was; cells were dieing so slowly at the end.

This is similar to what happens when someone takes antibiotics. The typical course lasts for 10 days, but you’ve killed enough of the bacteria to loose the symptoms of sickness after two or three. Those final few that remain are the most resistant to the antibiotic, and if you don’t kill them then, once you stop taking the antibiotic, they’ll start to grow and replicate and you’ll end up sick again with a new, antibiotic-resistant population of bacteria.

I thought that using the VAMP model for the demonstration worked very well. The sound of the cells popping up faster and faster with exponential growth seemed to help amplify the visual effect, and make the whole thing more real. And during the decay phase, having that last cell hang on, seemingly forever, really helped convey the idea that bacteria can be extremely persistent.