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With Friends Like These …

By (September 1, 2013) No Comment

Bacteria: A Very Short Introduction
By Sebastian G.B. Amyes
Oxford University Press, 2013

BacteriaFrom bubonic plague in the 14th century to hospital-acquired staph infections today, humanity has never faced a shortage of maladies. Earth supports an abundance of things that can make us sick—viruses, mutations, even exposure to chemicals and radiation—but the overwhelming number of our afflictions are bacterial. Our common fear of catching infections has resulted in pharmacies and supermarkets stocking innumerable novelties that boast of their ability to ‘kill 99.9% of germs and bacteria.’ But are we losing sight of the fact that bacteria are our friends too? Our, admittedly dangerous, tiny friends?

It’s difficult to call bacteria your friends if you don’t know much about them. While a quick wiki search would provide a dry and impersonal overview, Sebastian G.B. Amyes’ contribution to Oxford’s Very Short Introductions series, Bacteria, delivers a much more thorough, relevant picture of the life form with whom mankind has the most (usually unbeknownst to us) intimate relationship.

Bacteria are the simplest single-celled organisms in the world, capable of inhabiting almost every environment imaginable. As Amyes explains, bacteria are prokaryotic cells, different from eukaryotic (animal and plant cells) because of their much smaller size and lack of organelles—partitions that perform specialized tasks like energy production, metabolism, and reproduction. If you’ve taken a biology class, his descriptions seem like a quick crash-course review. But if you’ve never heard of RNA before, he lays it all out in a way that’s simple to understand. But Amyes’ book isn’t merely another Intro to Biology. Instead Bacteria: A Very Short Introduction thoroughly dramatizes the history of humanity’s interaction with those tiny cells, provoking a strong feeling of humility, and the sense that mankind really isn’t at the center of history. As Amyes explains early on:

It would be understandable if we thought that humans were the principal species on this planet and that we now live in the era where mammals dominate….The reason is that we tend to classify each era with what we can easily see around us or from what paleontologists have reported and placed in museums of natural history for us to marvel at. The truth is there has never been any dominant organisms other than bacteria and that this planet has been in the ‘Age of Bacteria’ almost from the beginning when life emerged.

If it weren’t for bacteria, our ancestors wouldn’t have been able to preserve products like milk or dispose of inconveniences like sewage, and we’d currently be living in a world without cheese and without the marvels of septic systems. We’d also be living in a world with a drastically small amount of edible food. Our guts contain about 500 species of bacteria that help us digest molecules like carbohydrates. The only drawback? The occasional outburst from our back end. A periodic case of flatulence is worth it though considering that “we would need to ingest 30 percent more food to maintain our body weight if we did not have bacteria fermenting in our gut.” Bacteria also play another vital role: by colonizing your insides they prevent harmful infections from making a home inside of you. When these beneficial bacteria fail however, other bacteria can begin to play a new, more sinister role in your body. If you’ve ever had food-poisoning, you’re already familiar with this undesired colonization. While the infections that cause you to spend a day or two in the bathroom are usually self-limiting and clear up on their own, there are other infections that can be harder for the body to fight off. These infections require some outside help.

Even if you’ve got the best immune system in the world, you’ve probably been prescribed antibiotics at some point to clear up that bad bout of strep throat or that annoying sinus infection. At the time that they were prescribed, you were probably just thankful to hear your doctor say that there was a way to cure you. After suffering from such an affliction, it’s hard to picture life minus this panacea. But do you actually know what those little pills, or that bubblegum pink liquid is doing inside of you?

bacteria (1)Since antibiotics were first prescribed, starting with penicillin in 1941, many people, including doctors, operated under the misconception that they could be used to treat both bacterial and viral illnesses. But antibiotics are very specific. They are chemicals that bacteria and fungi create as metabolic by-products to hinder the other species around them, creating less competition for space and resources. These chemicals affect other bacteria by doing one of two things: either preventing them from multiplying or actually destroying them. Most do the former, thereby stopping the infection from spreading within the body and allowing the immune system to get in and finish the job. They do this by stopping the manufacture of protein (and therefore DNA replication). The reason they don’t work against viral infections is that viruses are something else altogether; unable to replicate on their own, they are a bundle of DNA surrounded by a protein coat that inject their DNA into other cells. Those cells then use their own proteins to replicate copies of the virus, copies that later burst from their host cell (picture a micro-scale version of Alien). Since viruses can’t replicate on their own, antibiotics do little to stop them, and their use becomes completely extraneous. A viral infection will only go away with time and rest.

If you think taking antibiotics for a cold to cover your bases doesn’t have any side-effects think again. The unnecessary use of antibiotics can cause undesired consequences. In his New Yorker article “Germs are Us,” Michael Specter relays the idea of Martin J. Blaser, chairman of the Department of Medicine and professor of microbiology at the New York University School of Medicine, that bacteria might actually be more beneficial than harmful to us—that all our efforts to eradicate them through chemical warfare might actually be causing us to grow sicker, rather than healthier. The main bacteria Specter discusses is Helicobacter pylori, the cause of stomach ulcers. In 1982 the medical community discovered H. pylori and made every attempt to eradicate it from the stomach. For the most part it succeeded. It wasn’t until the last fifteen years that Blaser’s research group began to realize that H. pylori was actually helpful to children and that all the efforts to get rid of that particular bacteria could be causing even worse health effects.

And H. pylori isn’t the only bacteria being wrongfully evicted from its home. In Specter’s article, Blaser voices the possibility that the increasing rates of asthma, allergies, and sinusitis could be due to the high use of antibiotics – since antibiotics are not selective about the bacteria they kill in the body, they end up killing many of the species that help prevent illnesses. So the question Blaser asks is whether the premise behind antibiotics use is even sound. Maybe we shouldn’t be trying so hard to kill bacteria. Maybe we should be trying to colonize good bacteria within our bodies to prevent the bad bacteria from taking hold. This doesn’t mean that we should stop taking antibiotics altogether—it simply means that we should stop overprescribing them.

Still not convinced to put down those pills when you have a cold? In addition to killing the good bacteria in your body, antibiotics can start to become ineffective against the ‘bad’ bacteria if used incorrectly. If they are prescribed in an insufficient dose, they can kill off most of the bacteria but leave behind a few individuals that may have a mutation, causing them to be less affected. These individuals will then reproduce and recolonize the body. During the re-colonization, these survivors can mutate further, snowballing the bacteria’s resistance to the antibiotic that used to eradicate it. As Amyes explains:

This kind of mutational resistance is the reason why doses of antibiotic have to exceed a concentration threshold to prevent the mutants surviving; this has more recently been described as the ‘Mutant Prevention Concentration’.

If antibiotics are prescribed in too low a dose and bacteria build up a resistance to it, the only way to get rid of the infection is to go back to the drawing board and find a new antibiotic that the bacteria haven’t yet built up a resistance to. Finding this antibiotic is the tricky part. Antibiotics are generally split up into two categories: those that treat gram-positive bacteria and those that treat gram-negative. The two different gram categories refer to whether or not the bacteria retain a crystal violet stain; gram-positive bacteria retain the dye due to the structure of their cell wall, gram-negative do not. While there are some antibiotics that treat infections caused by both kinds of bacteria, most antibiotics usually treat one or the other. So the first step is determining which type of antibiotic is needed for the particular infection. The second (and much more difficult) step is finding an antibiotic that is safe to use. There are plenty of antibiotics available that are effective at killing bacteria. However they range in their ability to kill. Some antibiotics are broad-spectrum and able to kill many different species of bacteria while others are extremely narrow-spectrum and only kill a specific type of bacteria. While both spectrums have their advantages (broad-spectrum are able to clear up multiple infections at once but narrow-spectrum won’t upset your body’s natural flora balance), finding the balance between the two for a specific situation can be difficult. Similarly, it becomes difficult to find an antibiotic that will clear up the infection without damaging human cells. Any antibiotic used has to be able to kill bacteria while only mildly affecting human cells. This challenge is so enormous that “many pharmaceutical companies are now reluctant to invest in new antibiotics [because] the difficulties in discovering new antibacterial drugs that are safe enough to be given to clinical patients are immense.”

This problem is further compounded by the fact that bacteria are able to communicate with each other. Within a colony of bacteria, a phenomenon called quorum sensing takes place. Bacteria can release chemicals that, when they come into contact with a receptor on another bacterium, trigger the activation (or deactivation) of a gene in that particular bacterium. That bacterium then produces the same chemical, causing its neighbors to go through the same process. As the population grows, more chemical is released and more bacteria have their genes switched on or off. The ability to communicate is extremely useful to a colony of bacteria when antibiotics, particularly the ones that prevent cell reproduction, are introduced because the colony can send out the signal to stop multiplying and enter a dormant stage until the antibiotic dissipates. The ability of bacteria to communicate isn’t limited to individual colonies, though. Bacteria have an extra molecule of DNA that remains independent from the rest of their chromosome, called a plasmid. This plasmid is able to replicate and transfer from one bacteria to another. Thus if one species develops a resistance to a certain antibiotic it can pass on this resistance to a different type of bacteria if the two come in contact. This has happened when clinical bacteria (those that cause disease in humans) have come into contact with environmental bacteria. In the 1990’s Enteroccus strains, responsible for scads of infections, became increasingly resistant to Vancomycin, the antibiotic produced by the bacteria Streptomyces. The use of plasmids was suspected when three isolated genes were found in Enterococcus faecium that resembled the same genes that kept Streptomyces safe against their own antibiotic.

bacteria blueThough the developing resistance of bacteria is hardly something that affects our day-to-day lives, it’s something that everyone bears the responsibility of thinking on. Not only have antibiotics helped us treat infections, they have also decreased the risk of death from infection, increasing our life expectancy by ten years. This ten year difference is huge “compared to [the] two-year increase in life if all cancers were curable.” If we do not want to lose those ten extra years of life we need to start taking the necessary steps to prevent bacteria from becoming resistant to the antibiotics that still work. It seemed fitting that right after I finished reading Bacteria I came down with a bizarre illness that left me feeling so awful I dragged myself to the doctor’s office. After examining me and listening to a description of my symptoms the doctor told me, quite frankly, that she wasn’t sure what I had, but that she would prescribe me antibiotics just in case. I was a good patient and took my medicine as I was told, but I couldn’t shake that feeling of doubt, and guilt, that maybe I shouldn’t be taking antibiotics if I wasn’t sure I needed them. What if I was somehow contributing to one of the World Health Organization’s biggest problems?

Though I doubt I’ve caused the next big epidemic, these are the types of questions that will have to be raised about medical practice around the world. If the problem of resistance continues to escalate, Amyes reckons that medical procedures will have to start being assessed in terms of need vs. risk, cutting down on the amount of elective procedures that can take place. If this happens, what will we do without plastic surgery?

Despite this potentially grim future, there is hope. With modern genome sequencing scientists are able to map all of the genes in a bacterium. By studying and learning what causes the resistance-related genes to switch on there is the possibility that we could again make them susceptible to antibiotics. Even more importantly we could figure out which genes make bacteria a threat within our body and turn them off, allowing us to treat infections without having to use any antibiotics at all.

Regardless of how we end up dealing with bacteria in the future—whether we use new antibiotics, alter their genomes, or try to encourage the growth of the species we have a good relationship with—we will never stop interacting with them. The vast numbers of different species (known and as of yet undiscovered) guarantees this. Though many of our future interactions may end up being harmful, many more of them will probably allow us to adapt and survive. If that’s the case we certainly have a lot to learn from them about getting by in our constantly changing world. Maybe it’s time we put down that antibacterial soap and tried to rekindle our age-old friendship.

Frances Richardson
is a science writer and a biochemistry student at the Colorado School of Mines.