Viruses turn the tables on their bacterial hosts

Many species of  bacteria – including those that infect humans – are themselves threatened by parasites and predators. A large group of viruses called bacteriophages are known to infect bacteria. On infection, the phage transfers its DNA to the bacterial cell, hijacks the bacterial DNA-replicating machinery to make multiple copies of itself, and then escapes by killing the bacterial cell.

Bacteria have in turn evolved a variety of immune mechanisms to protect themselves against invading phages. About 40% of sequenced bacterial genomes contain a set of CRISPR/Cas genes. These include a set of genes encoding Cas proteins as well as CRISPR loci, which are arrays of short repeats separated by highly variable ‘spacer’ sequences.

These spacer sequences are identical to sequences present in phage DNA. They are transcribed into small RNA molecules called crRNAs, which, with the help of the Cas proteins, bind to and cause degradation of the invading phage DNA. However, a recent study published in Nature has discovered a novel CRISPR/Cas system – not in a bacterium, but in a bacteriophage.

This bacteriophage, called ICP1, attacks a strain of the cholera pathogen Vibrio cholerae. The authors demonstrated that the CRISPR/Cas system in the bacteriophage is fully functional and targets a region of bacterial DNA that is responsible for defense against the phage. Not only is this an example of a supposedly bacterial immune mechanism being used by a phage, but it appears that the phage uses it to counter an entirely different bacterial immune mechanism. This host vs. pathogen arms race suddenly looks a lot more interesting.


Bacteria Cooperate to Survive Overcrowding

For any bacterium, whether living deep in the ground or infecting a human body, overcrowding is one of the greatest threats it faces. A tightly packed environment means a shortage of food, competition for the best spaces, and the accumulation of toxic wastes excreted by its neighbors. And since many species of bacteria multiply very fast – a well-fed Escherichia coli cell can split in two every twenty minutes – overcrowding is almost inevitable.

Nevertheless, bacteria exist all around us, often packed to densities of billions in a single gram of soil. It’s hardly surprising that many scientists have wondered how these creatures manage to survive in such crowded conditions.

Now a joint study by Korean and American biologists has shown that not only do bacteria sense when their surroundings become severely congested, but that the bacterial community works together to help every bacterial cell survive the resultant stress. This involves a process named quorum sensing, by which bacteria can detect and respond to others of their kind.

Imagine every bacterial cell slowly releasing a chemical signal into its surroundings – a cell’s way of declaring ‘I am here’. As the environment grows steadily more crowded, more and more cells pump out their signal into a small space. When the amount of chemical signal present in the surroundings exceeds a certain level, indicating that a large number of cells are present, the quorum sensing system detects this change and directs all the cells to switch certain genes on or off, leading to a coordinated change in their behavior.

Glow-in-the-dark bacteria provide a classic example of the value of quorum sensing. Since a lone bacterium would not glow brightly enough to be noticeable, it keeps its light-producing apparatus switched off most of the time. But as soon as many such bacteria get together, all of them are simultaneously activated, producing a glow that is visible from afar.

In this case and others, bacteria use quorum sensing to avoid wasting energy. Though scientists guessed that quorum sensing might also help bacteria survive the stress of living in a crowded environment, this had not been demonstrated until now.

The study, published in the October issue of the Proceedings of the National Academy of Sciences, tested this idea and found it to be true. Researchers grew three species of bacteria under conditions that forced them to excrete ammonia as a waste product. Ammonia is toxic, and as the bacteria multiplied, the ammonia around them accumulated to potentially lethal levels.

However, as soon as the environment grew dangerously crowded, the quorum sensing system triggered all the bacteria to produce an acid called oxalate. This oxalate was released into the environment where it reacted with ammonia to form a harmless product, allowing the bacterial population to survive far longer than it would otherwise have.

This finding is particularly intriguing to scientists interested in social behavior, for it raises the possibility of interesting community dynamics among these bacteria. Would some bacteria cheat the rest by not producing any oxalate, instead surviving on the efforts of others? Over time, would the community evolve ways to punish these cheaters?

Even more interestingly, some of the bacteria used in this experiment are agents of disease in plants and humans, and the authors suspect that producing oxalate may help them survive the defenses of their hosts. If this is true, it might open the doors to a new strategy for treatment: one based not on killing bacteria, but on allowing them to crowd themselves to death.

Skin bacteria may protect you from disease

The human body is home to a vast number of bacterial species; in fact, it is thought that the number of bacterial cells in a human body far outnumbers the human cells themselves. Many of these bacteria live in the gut, while others live in saliva, the inside of the eyelids, or the skin.

While most of them have no known effect on us, some are useful to their human hosts. For example, several studies have suggested  that gut bacteria help our immune systems protect us against pathogens. A recent paper by Naik et al. in Science suggests that at least some of the bacteria living in our skin do the same.

These authors found that ‘germ-free’ mice without resident bacteria have reduced levels of interleukins (chemicals produced by white blood cells that help fight infections) in their skin tissues. When bacteria were introduced into the gut of these mice, interleukin levels in the gut increased, but levels in the skin did not. On the other hand, when a species of bacteria that normally resides in skin was introduced into the skin of germ-free mice, the interleukin levels in the skin increased, as did the immune response to the parasite Leishmania major.

It has long been known that gut bacteria produce vitamins that are important for human health. In recent years, a variety of studies have linked resident bacteria to obesity, disease, prevention of allergies, and even behavior. The finding that bacteria in our skin may be important for the human immune system is another step in understanding the importance of this vast and diverse population of cells.