Mycobacterium tuberculosis is the cause of tb, and is still a major health problem worldwide. There are a class of proteins that have no known functions, called the PE-PGRS family of proteins. They may be fibronectin binding proteins (fibronectin is one of those things that holds us together at the cellular level), they are involved in disease because if you delete some out Mycobacteria don’t grow as well, and they could be variable surface antigens that allow the bacteria to avoid being seen by our immune system.

Regardless of what it is actually doing, the phages like it. Several of the Mycobacterial phages contain PE-PGRS proteins, suggesting, again, that the phages are helping their hosts cause disease.

I had to rant about this. In phage P22, Moak and Molineux showed that gp7 is a murein hydrolase, the enzyme that breaks down the peptidoglycan layer and allows the phage to enter the host [here’s the paper]. Cool, we can find gp7, and annotate it is a Phage murein hydrolase. Here’s the snag. The original paper doesn’t have the DNA or protein sequence. Well, we go find gp7 in the genome [here’s the P22 genome in GenBank] and there is a gene called P22gp07, whose protein sequence starts “MQIKTKGDLVRAALRKLGVASD….”

However, if we look for P22 gp7 not in the genome, we find a completely different protein, whose sequence starts “mlhaftlgrk lrgeepsype…”.

Which one is the real gp7, and which one is the interloper. Of course, the people that annotated the genome just started with gp1 at the start of the genome, and incremented. While that’s one way to do it, it completely screws up anyone trying to use historical literature to annotate genomes.

Caveat emptor!

Image credit: http://www.deskpicture.com/DPs/Nature/Animals/hummingbird.jpg

As I’m sitting outside Café Vita and getting ready to work on phage subsystems, I can’t avoid being distracted by this number of bees and hummingbirds surrounding me. I have never had such a close view of a hummingbird. Because phage subsystems are keeping me still, these birds are totally peaceful around me. I am getting a really close view of hummingbirds working on sucking flowers. I have never noticed their beaks before. They are really interesting–well adapted to their feeding style (read about co-evolution of hummingbirds and their favorite flowers). And  because phage subsystems are keeping my mind busy, I can’t help but draw an analogy between phage modules and bird modules.

The hummingbird has several modules: a flight module (the unique wings),  a feeding module (i.e., the beak), a body module, etc. There may be other birds with same bodies but different beaks, same wings but different feet, and so forth. Phages are similar. Phage genomes, and subsequently their encoded proteomes, are modular: a set of clustered protein-encoding genes (Pegs) are dedicated to encode the phage heads (capsids); another set encodes the tails; a third set encodes host-specificity proteins, and so on. If a phage “decides” to “feed on” a novel bacterial host (for several reasons including the extinction of its old host), the phage will have to switch its host specificity. An entire phage can thus “exchange modules” with one that attacks the new host. For example, a phage in the human throat may face a crisis when the human host uses an antibiotic for a couple of weeks. The phage may be forced to switch hosts from streptococci (almost extinct after antibiosis) to bacteroides, for example (I’m just making this up). To do so, the phage needs proteins that are specific to Bacteroides.

Unlike birds, the phage cannot afford the slow process of mutagenesis and selection for evolving bacteroides-specific attack molecules. Instead, it would just “exchange” it with another phage that “knows how” to attack bacteroides but has been unsuccessful in replicating inside these anaerobic bacteria (probably due to bacterial immunity). The novel, re-invented, phage will keep the successful modules that replicate well (from the streptococcal phage) and the bacteroides-specific module from the less successful bacteroides phage.

This page has been created by Rob Edwards to guide phage fans, phage hunters, phage chasers, and phage watchers to phages as they are being annotated.