The Kinky World of Bacterial "Sex" (and why we should care)

An image of Clostridium difficile,
a potentially deadly bacteria.

C. diff. It's a name that may not mean much to the layperson, but to any health care worker, it causes shuddering and trembling.

Just ask my mom, who is a hospice nurse. She has a patient who has been afflicted with this nasty (and sometimes deadly) bacterial infection for weeks now. It can be resistant to most antibiotics, and is also quite resistant to destruction. Killing it requires bleach; soap and water or alcohol-based hand rub don't do a thing. C. diff is also very infectious, so my mom's patient has unfortunately had to be under isolation precautions this whole time. Which for anyone would be awful, but if you are in your last days of life, being isolated from the world - and having anyone who entered your world have to gown up and wear gloves - would be terrible. (At least I think so.)

So what exactly is C. diff, and what makes it so evil (to us at least)? Here is a bit about this robust bacteria, from the Mayo Clinic's Web site:

"Clostridium difficile (klos-TRID-e-uhm dif-uh-SEEL), often called C. difficile or C. diff, is a bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon. Illness from C. difficile most commonly affects older adults in hospitals or in long term care facilities and typically occurs after use of antibiotic medications." (Source: Mayo Clinic)

Bacteria can be beautiful -
and also dangerous.

That all said, bacteria are fascinating little buggers. (Not to mention beautiful under the microscope, as you can see from the picture at left.) And they are not all bad. There are bacteria in our bodies that are quite helpful to us, in fact. Bacteria can also be highly adaptive, which makes them all the more interesting - and potentially dangerous, when it comes to certain species.

One of the major issues facing health care today is MDROs - Multi-Drug Resistant Organisms. This includes several kinds of bacteria (such as Vancomycin-Resistant Enterococci, or VRE; and Methicillin-Resistant Staphylococcus aureus, or MRSA; as well as C. diff). As you can probably tell from the names, these organisms are resistant to specific drug treatments - the antibiotics vancomycin and methicillin, respectively, in the cases of VRE and MRSA.

But let's step back for a moment. How do antibiotics work? Or rather, how are they supposed to work? Antibiotics are separated into different classes depending on how they affect bacteria. For example, antibiotics can target a bacteria's:
1. Cell wall
2. Cell membrane
3. Essential enzymes

Antibiotics, when they work, cause destruction of the bacteria via one of these targeting mechanisms. Which is how they make us well again.

As I said, though, bacteria are highly adaptive. They can undergo "evolution" - favorable DNA changes - very rapidly, enabling them to resist an antibiotic's targeting mechanism. Examples of these rapid adaptations include:

1. No longer relying on a glycoprotein cell wall
2. Enzymatic deactivation of antibiotics
3. Decreased cell wall permeability to antibiotics
4. Altered target sites of antibiotic
5. Efflux mechanisms to remove antibiotics
6. Increased mutation rate as a stress response

(Thank you, Wikipedia, for the very succinct list above.)

Anyone who has read much about evolution, though, knows that this process is usually a very slow one: favorable DNA mutations gradually accumulate over time via reproduction and the passage of these favorable mutations down to offspring.

But bacteria are a little, well, different in terms of their DNA-transferring and reproductive capabilities. And these differences are what enable them to rapidly exchange DNA mutations in an expedited manner. How does this work? Well, let me explain.

Bacteria have not one, not two, but THREE methods for sharing DNA. This is in addition to an extremely rapid method of asexual reproduction called binary fission. I will explore each of these in detail (with pictures, of course).

Enter the world of bacterial "sex" ...

1. Conjugation. (See images, and explanation, below.)

Diagram of bacterial conjugation.

Bacterial Conjugation:
An image of the sex pilus

Conjugation is the closest that bacteria get to mating (i.e., sex). What happens is that one bacterial cell, termed the "donor," produces a cellular protrusion called a sex pilus. The sex pilus attaches to the "recipient" cell, and brings the two cells together. DNA is then replicated and transferred across the cell membranes, from the donor to the recipient. (Note: the donor possesses what is called an "F factor" - this is what enables it to transfer its DNA to the recipient. This F factor can also be transmitted, allowing both cells to then be donors.) This method of gene transfer can transmit antibiotic resistance from one bacterial cell to another. 

2. Transformation. This is the process by which a bacterial cell basically absorbs DNA from the environment through its membrane, incorporates the exogenous (outside) DNA into its own, and then expresses those new genes. The new DNA can either be incorporated into the bacteria's circular chromosome, or as a separate circular piece of DNA called a "plasmid." (See the diagram below.)

Diagram of bacterial transformation.

An electron micrograph, and a diagram, of a bacteriophage.
This is called a T4 bacteriophage.

3. Transduction. This process is a bit more complicated to explain, as it involves not only bacteria, but bacteriophages (aka "phages"). Phages are little viruses that infect bacteria. (Yes, bacteria are subject to infection, too.) What happens is that these bacteriophages attach to the bacteria, inject their phage DNA, and the phage DNA takes over the cellular machinery of the bacterial cell. Rather than meet its own needs (i.e., produce bacterial proteins), the bacterial cell begins to express the phage genes, producing new bacteriophage components. These phage components are assembled, again with the help of the bacteria's cellular machinery. Eventually, the bacteria lyses (breaks open), releasing the little viruses. Those new viruses can then go infect other bacterial cells. Sometimes, a piece of bacterial DNA gets "stuck" in a baby bacteriophage. So that when that bacteriophage goes on to infect another bacterial cell, the previous (and now lysed) bacteria's DNA gets injected and incorporated into the new bacterial cell. To complicate matters, there are two different cycles of bacteriophage infection: lytic and lysogenic. In the lytic cycle, the bacterial cell is immediately destroyed (lysed) and the new baby phages are released. In the lysogenic cycle, the phage DNA is incorporated into the bacteria and remains dormant until activated by certain environmental or stress conditions. So in order for a bacterial cell to share its newly incorporated DNA (from the phage infection), it must be in the lysogenic cycle. (For a graphic explanation of transduction, see the diagram below. Note that in Step 5, this is a second bacterial cell which is being infected.)

Diagram of bacterial transduction.

E. coli cells, some of which
are undergoing binary fission.

4. Binary Fission. So let's assume a bacterial cell has gotten a piece of DNA that gives it antibiotic resistance. It could transmit that DNA via one of the mechanisms above, to one bacteria at a time. But bacteria also reproduce, albeit asexually. And they are quite efficient at it. In a very simplified explanation, a bacterial cell replicates its DNA (which is in the form of one circular chromosome), the two chromosomes move toward opposite "poles" of the cell, and then the cell splits in half, forming two new cells. These divisions are measured in "generation times," which can be quite rapid. For example, under optimal conditions, E. coli's generation time is about 17 minutes. For Staphylococcus aureus, it's about 27-30 minutes. For S. aureus, that means that in 30 minutes, you go from 1 to 2 cells. After an hour, you have 4, then 8, 16, 32, and so on. It doesn't take long, then, to develop a sizeable colony. (Source: Online Textbook of Bacteriology)

So what does this mean? In essence, once one bacteria (or a few) accumulate DNA mutations that confer antibiotic resistance, there are myriad ways - conjugation, transformation, and transduction - to spread that DNA around. And then those bacterial cells "reproduce" (asexually) via binary fission and a whole host of nasty, antibiotic-resistant bacteria results. So when someone is given an antibiotic, the bacteria that are NOT resistant will die, but those that ARE resistant will live, and continue to reproduce. Not good. (At least, not for us. Good for the bacteria, obviously!)

The misure and overuse of antibiotics contribute to this problem by helping antibiotic-resistant bacteria survive, proliferate, and then spread to other people. This is especially an issue in hospitals and other health care facilities, such as nursing homes, where people are in close contact with each other (or contaminated objects come into contact with people) and patients are often immune compromised to begin with. 

Unfortunately, many of these so-called "superbugs" are resistant to multiple drugs, and are very virulent (infectious and harmful). And while there was a time several decades ago that saw wild discovery and development of new antibiotics, that has trailed off in recent years. In part because antibiotics are not seen as the "cash cows" that other drugs may be, and in part because the low fruit of antibiotic development has been plucked, it seems.

There is now an effort (at least of some sorts) to search for new sources of antibiotics, both natural and synthetic, as well as to curtail unnecessary use of antibiotics. But the "superbugs" are here to stay. For a good while, at least. And it's all thanks to the kinky world of bacterial "sex."