Antibiotics: what are they and how do they work?

The relationship between humans and microbes is a love-hate relationship. As we have seen in previous articles,1^{, 2} microorganisms, and especially bacteria, are important allies for us, since they live in huge numbers in our intestines and some of our food production depends on their help.

At the same time, however, it is necessary to keep bacteria and other potentially pathogenic microorganisms at bay, as they can be the cause of numerous diseases when they enter our bodies. One of the methods by which we can control the growth and invasiveness of bacteria is to use antibacterial drugs, particularly antibiotics.

In this article we will discover together how many different ways these substances can act in protecting us from the bacteria around us.

Antibacterial drugs and antibiotics

First, a few definitions: by antibacterial drugs we mean those chemicals that are toxic to bacteria at concentrations that are generally not harmful to humans. They have, therefore, selective toxicity. They can act as bacteriostats, blocking the growth of bacteria and facilitating their elimination by the body, or as bactericides, resulting in the death of the bacterium itself^.3

According to the original definition, antibiotics are called those antibacterial drugs produced by living organisms, such as bacteria or molds, while those produced in the laboratory are called antimicrobial chemotherapeutics. Today, however, even molecules with a natural origin are produced artificially, so they cost less and are safer. Moreover, by chemically producing them, they can be modified to make them more effective against bacteria, less harmful to patients, and easier to administer.

This allows for drugs that are also active against the now widespread resistant bacterial strains, which we will discuss in the next article. Since the distinction according to natural or synthetic origin is now outdated, therefore, in this article we will use the term antibiotics referring indifferently to either category (which is also what happens in everyday life when we go to the doctor or pharmacy).

The classification of antibiotics: the six categories

Antibiotics can carry out their action, bacteriostatic or bactericidal, with six different strategies^.4 Let’s look at them in brief!

1. Antibiotics that block bacterial wall production.

This category of antibiotics was the first to be discovered and investigated. In this regard, the contribution of Alexander Fleming, a Scottish physician who discovered penicillin, the progenitor of this family of bactericidal substances, is well known. Less well known, however, is the role of Vincenzo Tiberio, an Italian physician and researcher who predated Fleming’s studies by more than 30 years^.5

These drugs were originally discovered in liquid extracts of mold cultures, such as Penicillium notatum (cousin of the gorgonzola mold we discussed in a previous^article6), by observing how the presence of these molds prevented or limited the growth of bacteria in the vicinity.

From a molecular point of view, these antibiotics block certain chemical reactions necessary for bacteria to produce peptidoglycan, which is the main component of the wall that confers strength and solidity to bacteria. If the bacterial wall is not synthesized properly, any imbalance in the surrounding environment can be fatal to the bacterium, which finds itself without protection and can disintegrate.

Among the antibiotics with this mechanism of action, famous are the penicillins (such as penicillins G and V, or amoxicillin), the cephalosporins (very interesting their discovery by Italian doctor Giuseppe Brotzu in the waters of Cagliari harbor in the 1940s)⁷ and other antibiotics defined beta-lactams. Substances that inhibit bacterial wall production but are not beta-lactams include the following bacitracin, cycloserine, vancomycin, and fosfomycin (let’s not be fooled by the name “kitten”: they have nothing to do with kittens! The name takes the Greek root “myco” which stands for “fungus,” since the molds that produce them are fungi)

2. Antibiotics that block the production of essential vitamins

Historically, these substances were among the first chemotherapeutics used. As early as 1935, the antibacterial activity of a synthetic red dye was demonstrated. From there, studies continued until a new class of antibiotics, sulfa drugs, were developed that can block the production of folic acid in bacteria.

Folic acid, or vitamin B9, has an important role in DNA metabolism, especially in cells that are dividing rapidly. That is why its absence inhibits and blocks the multiplication of cells (both bacterial cells and our own, particularly during pregnancy).

These drugs are not a big problem for us humans, since we get the necessary folic acid from our diet. But for bacteria that have to produce it themselves, a blockage in the production chain becomes an insurmountable obstacle that prevents the cells from reproducing, thus ending the invasion of the host organism.

In addition to sulfonamides in the strict sense, such as sulfamethoxazole or sulfamethazine,para-aminosalicylic acid, dapsone, and trimethoprim (which slightly differently blocks the same vitamin B9 production pathway) also have similar action

3. Antibiotics that block protein production.

For a cell, protein production is a fundamental, most important process. Especially for rapidly growing cells, such as bacteria that are invading an organism. Blocking protein synthesis is therefore an excellent defense mechanism that we can put in place, but it is important to block only the production of bacterial proteins, without affecting the cells of the host organism that must be able to continue their work.

Fortunately for us, the bacterial structures devoted to protein production (the ribosomes) are slightly different from those in our cells. These small differences underlie the operation of a class of antibiotics that can block bacterial ribosomes and not allow them to produce all the proteins necessary for the pathogenic microorganism to reproduce.

Antibiotics such as streptomycin, macrolides (such as erythromycin, azithromycin, and clarithromycin), chloramphenicol, and tetracyclines (such as aureocycline, doxycycline, and metacyclin) work by this mechanism.

4. Antibiotics that block RNA production.

To make proteins, a key ingredient isRNA, which copies genetic information and carries it all the way to the protein production site itself. Blocking RNA synthesis therefore means blocking all the production work that lies downstream.

The antibiotics that act on RNA synthesis are rifampin andactinomycin D, now used only in cancer therapy since it was the first antibiotic to show a toxic effect even on cancer cells.

5. Antibiotics that block DNA duplication.

“To make a tree, it takes a seed,” the song sang. Thus, just as it takes RNA to make proteins, it takes DNA to make RNA. DNA is the repository of all genetic information inside the cells of all living things. To damage DNA is to ruin the ‘recipe book’ and thus prevent the proper functioning of the whole cell.

Some antibiotics act precisely at this level, such as mitomycin, which causes DNA damage and prevents DNA replication, a mechanism for which it is also used in cancer therapy. Instead, novobiocin and quinolones (such as ciprofloxacin) block the mechanisms of DNA duplication by preventing despiralization of the double helix, which remains supercoiled like the coiled wires of old telephones, creating a tangle on which the necessary proteins cannot work.

6. Antibiotics that weaken the bacterial membrane.

Last but not least are antibiotics that act on bacterial membranes, which are able to make them weaker and more permeable. These bind to the fats that make up the outer membrane of ^{Gram-negative} bacteria8 and act as a detergent, destabilizing the protective coating of the cell. An example of antibiotics in this category are polymyxin B and polymyxin E (colistin).

After seeing how the various categories of antibiotics work, in the next article we will discuss how bacteria escape such targeted attacks and see why it is such a big problem today. Don’t miss it!

Sources:

1. https://ingredients.saccosystem.com/probiotici-e-salute-un-viaggio-nella-letteratura-scientifica/
2. https://ingredients.saccosystem.com/fermentazione-cosa-e-tipologie-e-latti-fermentati-kefir/
3. https://www.my-personaltrainer.it/salute/antibiotici
4. Eudes Lanciotti, Introduction to Microbiology, 3rd ed., Zanichelli
5. Those who want to learn more about Vincenzo Tiberio’s life and scientific research will find a lot of interesting information with a quick internet search. There is also a documentary about it, titled “Vincenzo Tiberio, the man who discovered antibiotics.”
6. https://ingredients.saccosystem.com/muffe-e-batteri-per-produzione-formaggi/
7. https://it.wikipedia.org/wiki/Giuseppe_Brotzu
8. https://ingredients.saccosystem.com/batteri-di-tutte-le-forme-di-tutti-i-colori/