“One sometimes finds what one is not looking for.”

Alexander Fleming

What is Antibiotic Resistance?

Antibiotic resistance, which can also be called “antibacterial resistance”, refers specifically to the ability of bacteria to resist the effects of antibiotics. As a result, the antibiotics no longer kill the bacteria, and bacterial growth is not stopped. This means that standard antibiotic treatments become ineffective and infections persist, increasing the risk of severe consequences to the person and spread to others.

Antimicrobial resistance (AMR) is the ability of a microorganism to resist the effects of an antimicrobial medicine. (ref.01) (ref.02)

Antimicrobial medicines include antibiotics, antivirals, antimalarials and antifungals, which are used to treat microbial infections caused by:

  • bacteria (e.g. Escherichia coli, a common cause of urinary tract infections),
  • viruses (e.g. HIV),
  • parasites (e.g. Plasmodium species which cause malaria),
  • fungi (e.g. yeast),
  • and mycobacteria (e. g. Mycobacterium tuberculosis which causes tuberculosis).

How do bacteria become resistant to antibiotics?

Antibiotic resistance is not a new phenomenon. Although reported only since the 1940s, resistance has existed in nature for thousands of years. It has evolved as bacteria, fungi and parasites spontaneously produce antibacterial, antiparasitic and antifungal substances in order to survive in competition with these other species. In fact, this is how many of the antibiotics used today — for instance penicillin — were discovered. However, over the last 50 years, an increasing number of bacterial species have developed resistance to antibiotics. Moreover, genetic analysis has revealed that certain resistance genes have recently emerged as a consequence of over-use and misuse of antibiotics in medical and veterinary settings.

As the global consumption of antibiotics as well as international travel continue to rise, bacteria are mutating and exchanging their resistance genes at an unprecedented pace. Bacteria have the natural ability to multiply and change their genetic material (which we call “mutate”) very quickly, which can be seen as a survival mechanism that allows them to adapt to new environments. Every time we take antibiotics — or use them in animals — we create a selection pressure on resistant bacteria to survive and give them an opportunity to adapt to antibiotics.

Once bacteria have acquired the genetic mutations needed to survive in the presence of antibiotics (i.e. resistance to antibiotics), they spread their resistance to other bacteria through two main mechanisms called “vertical” or “horizontal” gene transfer (see figure). In fact, some bacteria can transfer resistance genes amongst one another very easily.

As a result, there is increasing concern about the rising numbers of antibiotic resistant bacteria that are isolated from human, animal, food, water and soil samples. Antibiotic resistance emerges as much in “friendly” bacteria (which populate our skin, our mouth, our intestines and other body areas without causing disease), as in pathogenic bacteria (those which cause disease in humans and animals).

* Bacteria harbouring a resistance gene (in red), which are in the minority before antibiotic treatment, survive exposure to antibiotics and become the most common bacterial population. Moreover, mutations (random changes) in the bacterial DNA may occur which favour its resistance to antibiotics, leading to the emergence of new resistance genes (in orange). In some cases, these resistance genes can be exchanged between bacteria (step 2), which eventually leads to multi-resistant strains – bacteria which are resistant to multiple types of antibiotics.

When exposed to antibiotics, the bacterial population is modified*

Modification of bacterial population when exposed to antibiotics

Antibiotic resistance: how does it work?

Antibiotic resistance occurs when microbes become resistant to one or more antibiotics that are used to treat infection.

Acquired resistance

Antibiotic resistance can be acquired through either the transfer of resistance genes from other bacteria, or through the spontaneous development of resistance mechanisms as a means of survival.

Gene Transfer by Vertical or Horizontal Transmission

Vertical transmission: mutation of a gene (red) during replication, giving the bacteria the ability to become resistant to the effect of antibiotics. These mutations are then passed on to subsequent generations, leading to a population of resistant bacteria.

Horizontal transmission: resistant genes are exchanged from one microbe to another.

Resistance mechanisms: how do bacteria resist antibiotics?

  1. Impermeable barrier: the bacterial cell membrane develops an impermeable barrier which blocks antibiotics.
  2. Target modification: modification of components of the bacteria which are targeted by the antibiotic, meaning the antibiotic can no longer bind properly to its target in order to destroy the bacteria.
  3. Antibiotic modification: the cell produces substances (usually a protein called an “enzyme”) that inactivate the antibiotic before it can harm the bacteria.
  4. Efflux pump mechanism: the antibiotic is actively pumped out of the bacteria so that it cannot harm the bacteria.