Antibiotics

One hundred years ago, a third of all adult deaths and half of all childhood deaths resulted from infectious diseases such as those caused by bacterial pathogens. By the start of this century, those numbers had fallen dramatically altogether, and those attributed to communicable diseases even more so, with only 7% of childhood deaths credited to these illnesses. This was possible in part due to the appearance of antibiotics.

The meaning of antibiotics

Antibiotics are antimicrobial chemicals produced in nature by bacteria and fungi. These chemicals help the producing organism by killing or inhibiting its microbial competition by limiting resources like water or food, especially in environments where these resources are less available. These chemicals have had an enormous impact on therapeutics over the past decades because of their proficiency in exclusively killing bacterial cells.

Antibiotics are some of the most important drugs used in modern medicine. These drugs are used to treat communicable diseases caused by bacterial pathogens. When used in therapeutics, antibiotics can be a natural antimicrobial product made by bacteria/fungi or, more often, at least partially synthetically enhanced in labs by chemical processes to be made more effective. These drugs can also be fully chemically synthesised in labs based on structures of functional natural antimicrobials.

Antibiotic classification: how do antibiotics work?

Antibiotics can be classified into two main categories which work by either killing the bacteria directly (bactericidal), thus resolving its harm, or stopping its growth and ability to multiply (bacteriostatic). In the latter option, the bacteria population remains the same in the infected host, giving the host's immune system a bigger chance of fighting off the infection. These drugs can accomplish this by targeting different critical aspects of the growth or metabolism of bacteria which can include:

• Bacteria cell wall synthesis
• Cell membrane proteins activity
• Bacterial DNA replication or protein synthesis

However, one of the most popular targeting methods of antibiotics is interfering with the bacterial cell wall. This organelle comprises long structural polymers called peptidoglycans, which are assembled using cross-links that form between them. Some antibiotics, like penicillin, work by preventing these cross-links from forming because they inhibit the enzymes that build them.

Successfully targeting the bacterial cell wall using antibiotics like penicillin requires the infecting bacteria to be growing. Only when the bacteria grow, do they need to expand their cell wall, and this process can be disrupted with penicillin. In these instances, growing bacteria create holes in their cell walls using autolysins enzymes. This allows the cell wall to stretch and binds newly synthesised peptidoglycans. However, in the presence of penicillin, these chains don’t occur. As new holes appear in the growing bacteria, its cell wall becomes progressively weaker. This weakening eventually leads to the bacteria cell bursting from the osmotic pressure potential of its water content.

Fig. 1 - Penicillin killing a bacteria

The importance of antibiotics

Antibiotics have become incredibly relevant therapeutic tools in the last century, and they significantly help reduce the incidence of infectious diseases caused by bacterial pathogens.

The importance of antibiotics stems from the fact that they only target bacterial cell components and not those present in the eukaryotic infected host, like human cells.

Other antibiotics might target proteins specific to the bacterial pathogen that can't be found in humans. This selectivity ensures that antibiotics' actions are limited to the bacteria and not us, which is why antibiotics are so widely used.

A common misconception is that antibiotics can also be used to treat viruses. Viruses are not bacteria, so they do not have bacterial antibiotic targets like cell walls. In fact, viruses aren't cells; some scientists defend that they aren't even living beings since they need the host’s transcription and translation machinery to replicate. As such, antibiotics don’t affect viruses and can’t treat viral illnesses like the common cold, flu or COVID-19. Only antivirals, a different kind and less common type of drug can effectively treat viral illnesses.

The different types of antibiotics

Antibiotics are usually classified according to their chemical structure. According to the CDC, the following types of antibiotics are recognised:

Antibiotics can be more generally classified according to the spectrum of bacterial pathogens they can treat.

• Narrow spectrum antibiotics, like penicillin G, can only target and kill a few bacterial species, mainly gram-positive bacteria.
• Others like tetracycline are effective against many types of bacteria (gram-positive and gram-negative) and are designated as broad-spectrum antibiotics.

Just as antibiotics became a household tool for modern medicine in the last 70 years, their over-use and misuse are now increasing one of medicine’s most feared dilemmas, the emergence of antibiotic-resistant untreatable bacteria.

Antibiotic resistance in biology

Antibiotics are becoming increasingly ineffective at killing the bacteria that were once susceptible to antibiotics. This results in bacteria not being inhibited by frequently used antibiotics, also known as antibiotic-resistant bacteria. Antibiotic-resistant bacteria are turning into one of the most serious healthcare problems of the 21^st century because they will hinder our ability to treat infectious bacterial diseases effectively.

Since the appearance of penicillin in the last century, more and more bacteria have become resistant to all antibiotics discovered and available today. The occurrence of antibiotic-resistant bacteria is a naturally occurring phenomenon. Bacteria’s DNA, like all other organisms' DNA, mutates. When DNA mutates, it can result in the bacteria producing different proteins that can confer resistance to a certain antibiotic.

The existence of these bacteria is a phenomenon best described through natural selection. However, the systematic overuse of antibiotic therapeutics is now driving this process and accelerating natural selection, causing resistance-conferring genes to have a bigger chance of spreading. Bacteria with more favourable traits, like countering antibiotic action, will survive under a selective pressure environment created by antibiotic overuse. These bacteria will have the opportunity to spread their genetic material to other bacteria. Over time, the bacterial population will increasingly be composed of antibiotic-resistant bacteria, and very dangerous strains of bacteria like MRSA (methicillin-resistant Staphylococcus aureus) and Clostridium difficile (C. difficile) will emerge.

The antibiotic selective pressure exerted over bacteria has particularly rapid effects because bacteria are highly promiscuous in exchanging genetic material. The transmission of antibiotic resistance genes can happen through two mechanisms:

• Vertical transmission – genetic material is passed on through reproduction whereby the bacterial cell divides by binary fission and passes on the mutated genes to the daughter cells. Bacteria divide so frequently that millions of copies can be made in hours.

• Horizontal transmission – genetic material (in particular plasmids) can be directly transferred between different species of bacteria through bacterial conjugation, whereby a tube connects two bacteria and allows the material to be copied and transferred. This means that a gene that confers resistance to an antibiotic can appear in one species and be passed to another species.

Fig. 2 - Bacterial transmission of genetic material

The spread of antibiotic-resistant bacteria will become an even more problematic dilemma, as the race is on to find new antibiotics before resistance is developed to the strongest antibiotics available now. In the future, addressing this issue will have to include reducing the opportunity of bacteria to develop resistance altogether through for example:

• Minimising the use of antibiotics and using narrow-spectrum over broad-spectrum antibiotics

• Reducing antibiotic usage in farming to prevent infections

• Ensuring patients complete their antibiotic treatment regimen, so there is no opportunity for resistance to appear in surviving bacteria.