Wednesday, February 28, 2018

Not Just a Passing Phage


Now let’s take a step back. Pathogenic bacteria. Antibiotic resistance. How do we evade this doom and gloom?

Well, someone is here to lend us a helping hand: the big, bad “bacteria-eater!”

In fancy (but, nonetheless cool) science mumbo-jumbo, this translates to “bacteriophage,” or just phage, for short. Funnily enough, phages were first discovered by two different scientists, in two different countries, around the same time! But considering that we now know that there exist more bacteriophages on Earth than stars in the galaxy, maybe it isn’t so astounding that two minds would stumble upon them simultaneously!

So, what exactly is this mysterious “bacteria-eater?”

A bacteriophage is simply a virus that infects bacteria. And just like our other favorite microbial “undead,” a bacteriophage is acellular, and thus not considered alive.

Photo by Drew March.
 But bacteriophages are not nearly as scary as zombies (save for the fact that some resemble microscopic spiders!) Rather, phages just boil down to a handful of proteins and your choice of nucleic acid for the assembly instructions. The DNA or RNA is kept within a hardy protein covering, studded with different surface proteins for some bling (and to perform important biological functions, of course! Talk about a two-for-one deal!) This is called the capsid or head of the virus.

Phages largely also have a slim protein tube or tunnel that nucleic acid dashes through to wiggle its way into a bacterium during infection. And in more complex phages, this tail sheath can be decked out with tail fibers: long, threadlike protein filaments that resemble the lanky, spindly legs of a daddy-longlegs!

Bacteriophages have breathtaking diversity! Some may be teeny-tiny, plain-Jane RNA phages with nothing more than a simple capsid and a hunk of RNA, while others may have gizmos and doodads such as baseplates, tail fibers, and an array of surface proteins sprucing up their already intricate capsid, out the wazoo!

But phages can be picky eaters (a phenomenon almost unheard of among college students!) For a phage to be able to grab onto a bacterium, there must be a painstakingly precise molecular interaction between a surface protein in the bacterial cell wall and the tail of the virus. Since this attachment is so tightly under lock and key, a given phage typically has an exclusive VIP list of hosts it can party with. Just look at “coliphages” like T2 and T4 that selectively infect E. coli.
 
Photo courtesy of  MicrobiologyBytes.
But once a phage has hitched itself a ride on a bacterium, it injects its DNA or RNA into the cell and right into a “choose your own adventure” book. If the environment is good to go, the nucleic acid launches its sneak attack and hijacks the cell to copy itself and use itself as a blueprint for new infant viruses. But the virus also has genes for the ace up its sleeve: lysosome. This enzyme is essentially a wrecking ball to a bacterial cell wall, all but obliterating it, to allow fledgling phages to burst free and infect nearby hosts. Since this option demolishes or “lyses” the host bacterium, it is fondly named the lytic cycle.

But the flip scenario is in an environment with a red flag, a bacteriophage will instead initiate stealth mode. In this undercover state, that is: the lysogenic cycle, the phage slips its DNA into the DNA of the bacterium so that when the bacterium divides future generations also get the bonus phage DNA. But if the environment were to somehow shift, it can activate the phage DNA, throwing the unsuspecting bacteria right into the midst of the lytic cycle! Espionage at its finest, if I do say so! But not all phages have these sneaky spy skills; rather, these tricksters get a special code name: temperate phages.

Although we can thank phages for a multitude of scientific discoveries and our comprehensive understanding of molecular biology, since their discovery was followed closely by that of Penicillin and thus the advent of antibiotics; we have rarely seen them in therapeutic use, especially in the western scientific community. But as more and more bacterial strains acquire handy-dandy antibiotic resistance, some scientists have begun turning to our friendly neighborhood bacteriophages!

Not only do bacteriophages mutate and evolve with bacteria, but there exist literally countless phages capable of lysing a single strain of bacteria.

Promising, no? Maybe the natural predators of bacteria should take the wheel!

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