How does resistance develop?

Antimicrobials act as a selective pressure on pathogens, forcing them to develop resistance mechanisms in order to survive. Some microorganisms are naturally resistant to antimicrobials, and are said to have intrinsic resistance. Others develop acquired resistance through genetic mutations or the acquisition of genes via horizontal gene transfer or mobile genetic elements such as plasmids. 

There are 4 main molecular mechanisms of antimicrobial resistance [3]: 

1. Reduced drug uptake
2. Drug target modification 
3. Drug inactivation 
4. Drug efflux

Click the on the image below to learn more about the different antimicrobial resistance mechanisms:

Figure 1: Illustration of the main antimicrobial resistance mechanisms used by microorganisms. While the image focuses on a bacterial cell, these mechanisms are also employed by other pathogens. For instance, viruses often evade antiviral drugs by acquiring mutations that modify the drug target. Additionally common antifungal resistance mechanisms include drug efflux and target modification, while parasites frequently use strategies such as drug inactivation, efflux, and target modification.

Organisms that are intrinsically resistant typically encode efflux pumps which help to transport the drug out of the cell, or have reduced membrane permeability which prevents the drug from entering the cell. Organisms that acquire resistance usually do so via mutations in genes that encode drug targets, drug transporters, or antimicrobial-modifying enzymes. Alternatively they may acquire novel antimicrobial resistance genes (ARGs) that function to modify the drug target, inactivate the drug, or efflux the drug [4].