Tuesday, December 21, 2010

Of Bread Molds, Bacteriophages, and Bug Brains: The Fight Against Infection

On a quiet morning in September of 1928, a brilliant but absent-minded microbiologist found that one of his Petri dishes containing colonies of bacteria had been contaminated with a fairly common mold that is usually found on bread and fruit. Rather than simply throw out the plate, the scientist noticed that there were no bacterial colonies growing around the mold—instead there was a clear zone around the mold that was completely absent of growth. Upon further investigation, he realized that the mold, called Penicillium notatum, was secreting a substance that inhibited growth of certain bacteria. This microbiologist, Alexander Fleming, had just discovered one of the most important substances of the twentieth century: penicillin.

Over the next few decades, several scientists worked on better understanding, purifying, and mass-producing penicillin. In fact, penicillin was an important force in World War II, saving as many as 15% of Allied troops with severe infections from battle injuries. Penicillin was, and continues to be, very important in handling bacterial infections. It was the first effective drug used to treat diseases such as gonorrhea, syphilis, or gangrene. However, penicillin cannot inhibit the growth of many types of bacteria and sometimes causes problematic side effects. As a result, there has been an assortment of semi-synthetic derivatives of penicillin produced (such as ampicillin and amoxicillin) that have a similar mechanism of action but can treat a wider variety of infections with fewer complications. Over the years, other antibacterials with different modes of action, such as erythromycin, mupirocin, and tetracycline, have been discovered, developed, and have saved countless lives.

However, all antibacterials have the same problem: bacteria can develop resistance. This means that a drug employed to treat an infection, especially if it is overused, is no longer effective. All antibiotics work by interfering with some aspect of the pathogen’s metabolism that is different from the host’s. But if a bacterium evolves so that some aspect of its metabolism is altered, a drug no longer works. The matter is further complicated because many bacteria can share genetic information, so that resistance can be passed from one species to another. The resulting bacteria can wreak havoc, since treatments are either ineffective, extremely expensive, or toxic to the patient.

This problem has propelled a search for the next generation of antibiotics. Many drugs so far have been found in nature, from common molds to plants to bacteria themselves. A great number are slightly altered versions of these natural compounds that somehow improve the original. But many of the most promising new antibacterials are being found in the strangest of places, most notably, cockroach and locust brains. Though an initially strange idea, it makes sense to look inside of insect brains for highly effective antibiotics with few side effects. Bugs tend to live in nasty environments teaming with all sorts of bacteria, so in order to protect themselves from infection, they produce substances that will kill off invaders and protect their delicate little nervous systems. Scientists have also turned to the seas for new antibacterials. Some marine invertebrates, such as the hydra or sponge, produce antibacterials that attack bacteria in completely new ways. Instead of using a regular molecule, they can use proteins to kill off pathogens.

Another unique strategy is the use of viruses to inhibit bacterial growth. Bacteriophages, which are viruses that infect bacteria, are perfectly safe in the human body and are very effective in killing off pathogens. Furthermore, they are highly specific and thus will not affect the “good bacteria” that are found in our bodies, which has been a problem with some commonly used antibacterials. Phage therapy is certainly not a new strategy, having been used for decades in eastern Europe, but it is only now being investigated for use in the United States. Research on phage therapy has been looking promising for treatment of highly problematic infections, such as those caused by methicillin-resistant Staphylococcus aureus (MRSA).

The twentieth century brought us the ultimate answer to Louis Pasteur’s Germ Theory (which states that many diseases are caused by microbes): antibiotics. Antibacterial drugs, from the mold-derived penicillin to the extremely toxic chloramphenicol, have revolutionized medicine and turned diseases that were originally a death sentence to completely treatable conditions. Hopefully, the twenty-first century will bring a new host of strategies that will fight pathogenic bacteria and keep us healthy.

Note: Though they are often used interchangeably, there is an important difference between antibacterials and antibiotics. Antibacterials specifically handle bacteria, whereas antibiotics take on any microbe (a better term is “antimicrobial”). In this article, I have opted to use both words, but never synonymously. See this Venn diagram for my completely unnecessary and by no means thorough explanation:

1 comment:

  1. Thanks for posting this article. I learned a lot--did not know about the bug brains, sponges and phages.... Fascinating stuff.