Allow me to preface this post series with a wholehearted acknowledgment of the beneficial role antibiotics have played, and continue to play, in fighting infections that might otherwise take limbs or lives. Before formal antibiotics, ancient and traditional cultures employed antibacterial herbs, tinctures, and even moldy bread, but regardless of the various methods’ efficacies, they were largely operating in the dark. They knew what worked, but not why it worked. When we use antibiotics today, we (mostly) understand what they are doing on a micro level, and we aren’t (ideally) just relying on hearsay, anecdote, and experimentation. This is a good thing.
So, how do antibiotics work, exactly? There are four primary routes taken by various antibiotics:
By crippling the microbe’s ability to fortify its cellular walls against external forces. Some antibiotics, like penicillin, prevent the target bacterium from manufacturing a substance called peptidoglycan that only bacteria use to construct cellular walls. Because animals don’t use peptidoglycan nor do our cells have “cell walls,” antibiotics don’t hurt our native cellular structures. Human tears actually contain lysozymes that also break apart peptidoglycan bonds in bacterial cell walls, much like antibiotics.
By binding to the protein synthesizing equipment inside the bacteria, gumming it up and interfering with its ability to arrange amino acids into proteins that perform vital roles. Tetracycline, a common antibiotic, binds to cellular ribosomes and interrupts an important step in RNA protein-sequencing. Luckily for us, human ribosomes don’t accumulate enough tetracycline to interrupt the sequence; bacterial ribosomes, however, accumulate enough to stop it altogether.
By preventing the bacteria’s synthesis of folic acid. Since all cells require folic acid and bacteria cannot absorb it from the environment, they must create their own. If something prevents its synthesis, the bacteria die. The sulfonamide class of antibiotics closely resembles para aminobenzoic acid, a critical component of the folic acid synthesis cycle. When bacteria mistake the sulfonamide for para aminobenzoic acid, they attempt to use the former to make folic acid. This doesn’t work and the bacteria eventually dies. Pretty devious, eh?
By targeting and interrupting the DNA replication process specific to bacteria. If a cell – any cell – is prevented from replicating its DNA, it dies. Ciprofloxacin is one antibiotic that targets DNA replication.
So, we’ve developed antibiotics that hit processes specific to bacterial cells while sparing human cells, and antibiotics that perform specific tasks and target specific species of bacteria. It all sounds pretty ironclad, yeah? There are some problems with antibiotics, though. Some very serious ones.
Foremost among them (at least in popular medical literature) is antibiotic resistance.
To understand antibiotic resistance, we must understand where most antibiotics come from. We derive pharmaceutical antibiotics from naturally-occurring bacterial weaponry, “natural” antibiotics manufactured and wielded by fungi, bacteria, and algae with the necessary genes in their ceaseless battle against other fungi, bacteria, and algae. Natural antibiotics and the bacteria the antibiotics are targeting have co-evolved over millions of years together. Just as the gazelle responds to the lion, and the lion to the gazelle, these microbes have also developed genetic counter-measures to enemy antibiotics. Written within their very genes are the tools to both produce and resist enemy antibiotics, and at least as far back as 30,000 years ago (and almost certainly many millions of years more, or for as long as bacteria have been battling each other), bacteria possessed the genes for antibiotic resistance. It’s been a lethal, ceaseless game of tit-for-tat against the backdrop of natural selection, with each side keeping the other in check.
Once we stepped in and began reproducing these antibiotics en masse, however, the delicate balance was tipped. Infectious diseases were hit pretty hard, and everyone hailed the great success of antibiotics. And they were a success, for the most part. The problem was the bacteria they were targeting kept evolving new defenses. And whereas “in the wild,” natural selection would usually produce a counter-counter-measure to the counter-measure and so on and so forth, we didn’t have that luxury. Our antibiotic pills weren’t going to adapt on their own. There was no selective force. We couldn’t just wait around for evolution to occur; we had to chemically alter the antibiotics to overcome the bacterial resistance. We had to laboriously and paintstakingly guide the hand of evolution ourselves. We had to engineer a selective force.
And so you have antibiotics like methicillin, which scientists created by modifying penicillin to get around bacterial resistance to penicillin. It worked, but only until bacteria like methicillin-resistant Stapphylococcus aureus (MRSA) emerged, and we had to start all over. Numerous other examples of resistant bacteria have surfaced as well:
- The infamous Clostridium difficile, commonly known as C. diff.
- E. coli.
- Certain species of Streptococcus.
- Certain species of Enterococcus.
- Certain strains of Mycobacterium tuberculosis.
Even those bacteria that do not endogenously possess the genes for antibiotic resistance can become resistant to antibiotics through a process called horizontal gene transfer, or HGT. HGT allows helpless bacteria to acquire genetic material from resistant bacteria that happen to be passing by. Through HGT, bacteria of one species can obtain antibiotic resistance from bacteria of another unrelated species. Acinetobacter baumannii, also known as multi-drug resistant acinebacter, is a common pathogen that obtained most of its resistances through HGT. In its cells, A. baumannii maintains multiple collections of foreign genetic material, kind of like a collector of weaponry from across the world. Oftentimes, the primary source of all this prime genetic material is a species of bacteria that poses no threat to humans but that wants to survive antibiotics just the same – and so develops numerous resistances which other, more dangerous species can pick up for free.
The big problem is that antibiotic resistance is a built-in feature of bacteria. It’s not going away. I mean, that’s what life does – it survives. And when the going gets tougher (when an organism is repeatedly subject to threats to its survival), that organism adapts and evolves and grows stronger. The more you produce the threat, the more you overprescribe antibiotics, the more you indiscriminately feed livestock antibiotics to promote faster growth, the quicker these resistances develop and spread.
Antibiotic resistance is a systemic issue, one that affects the global picture of health. It’s no doubt important, but there’s not a whole lot to do besides be aware of the issue (unless you’re a hotshot microbiologist actually working on new and improved antibiotics). There’s another problem with antibiotic usage, though, a hyper-local one that does impact us on an individual level and that we can hopefully successfully navigate. Next time, I’ll discuss that other unintended, but totally foreseeable, consequence of administering antibiotics in order to kill bacteria: the death of helpful bacteria living in the gut. And later, maybe in the same article if there’s enough time, I’ll go over strategies to combat the problems of antibiotics.
Thanks for reading this first part, and take care until next time. Let me know your thoughts in the comment section.