What Are AMR Genes and Why Are They a Threat?

Antimicrobial resistance (AMR) occurs when microorganisms like bacteria develop the ability to withstand the drugs designed to eliminate them. This resistance is driven by antimicrobial resistance genes, which provide the instructions that allow microbes to defeat medicines like antibiotics. As a result, once-treatable infections can become difficult to manage, increasing the risk of disease spreading.

The rise of AMR is a current global threat, directly causing an estimated 1.27 million deaths in 2019 and contributing to nearly 5 million more. This resistance complicates procedures like organ transplants and surgeries, as the medicines we rely on become less effective.

How AMR Genes Function

Antimicrobial resistance genes protect bacteria from antibiotics through several molecular strategies. One method involves producing enzymes that chemically alter or destroy the antibiotic. For instance, bacteria with bla genes produce beta-lactamases, which break down beta-lactam antibiotics like penicillin, rendering them inactive before they can harm the bacterium.

Another strategy involves altering the bacterial component that an antimicrobial drug targets. AMR genes can cause subtle changes to the shape of these targets, preventing the drug from binding effectively. The mecA gene in Methicillin-resistant Staphylococcus aureus (MRSA) produces a modified protein that methicillin cannot latch onto, allowing the bacteria to survive.

Bacteria can also physically prevent antibiotics from reaching their targets. Some AMR genes reduce the permeability of the bacterial cell membrane, limiting the entry of drug molecules. Gram-negative bacteria, for example, have a protective outer membrane that naturally restricts access.

A related mechanism is the use of efflux pumps, which are protein structures that actively pump antibiotics out of the cell. Encoded by specific AMR genes, these pumps function like cellular bilge pumps, expelling harmful drugs before they can accumulate to a toxic concentration. This allows the bacterium to survive in an otherwise lethal environment.

The Origins and Evolution of AMR Genes

The origins of AMR genes are both ancient and varied. Resistance can be intrinsic, meaning a bacterium possesses inherent traits that make it non-susceptible to a drug, such as lacking the cellular target an antibiotic is designed to attack. This form of resistance is a natural characteristic passed down through generations.

More commonly, resistance is acquired through new genetic changes, such as spontaneous mutations in a bacterium’s DNA. During replication, errors can occur, and a chance mutation might alter a gene in a way that confers resistance. If exposed to an antibiotic, that bacterium will survive and pass the new resistance gene to its offspring.

Many AMR genes have also existed for millennia in environmental microorganisms, particularly in soil. These microbes produce their own antimicrobial substances to compete for resources and have co-evolved with resistance mechanisms to avoid self-destruction. This environmental reservoir serves as a source from which disease-causing bacteria can acquire resistance.

The widespread use and misuse of antibiotics in medicine and agriculture has created powerful selective pressure that drives the spread of these genes. When antibiotics are used, susceptible bacteria are killed, while any resistant bacteria present are left to thrive without competition. This process selects for bacteria carrying AMR genes, increasing their prevalence.

Transmission Pathways of AMR Genes

While bacteria pass genes to their offspring, their ability to share genetic material horizontally with unrelated bacteria fuels the rapid dissemination of resistance. This process, known as horizontal gene transfer (HGT), allows resistance to spread quickly across different bacterial species.

One mechanism of HGT is conjugation, which involves direct cell-to-cell contact. One bacterium extends a tube-like pilus to another, creating a bridge to transfer a copy of a plasmid, a small piece of DNA often carrying AMR genes. This exchange allows a resistant bacterium to teach a non-resistant one how to survive an antibiotic.

Another pathway is transduction, which uses viruses that infect bacteria, known as bacteriophages. A bacteriophage can accidentally package a host bacterium’s DNA, including an AMR gene, into a new virus particle. When this virus infects another bacterium, it injects the resistance gene along with its own genetic material.

Bacteria can also acquire AMR genes through transformation, where they take up naked DNA from their environment. When a bacterium dies, its DNA is released, and other bacteria can absorb these free-floating fragments and integrate them into their own genomes.

These transfer processes are facilitated by mobile genetic elements, such as plasmids and transposons (“jumping genes”). These elements can capture and carry AMR genes, moving between a plasmid and a bacterial chromosome or between different plasmids. This can create multi-drug resistance cassettes that are transferred as a single unit.

Consequences for Public Health

The spread of AMR genes has direct consequences for public health. The primary impact is an increase in sickness and death from infections that were once manageable, as the failure of first-line antibiotics leads to more severe and prolonged illness. Drug-resistant pathogens are estimated to cause hundreds of thousands of deaths annually across the globe.

Treatment failures also drive up healthcare costs. They necessitate the use of second- or third-line drugs, which are often more expensive and can have more severe side effects. Longer hospital stays and the need for more intensive care contribute to a heavy financial burden on patients and healthcare systems.

The threat of AMR extends beyond treating common infections, jeopardizing modern medical procedures. Organ transplantation, joint replacements, and cancer chemotherapy all rely on antibiotics to prevent and treat bacterial infections. Without effective antibiotics, the risk of post-operative infections would make many of these life-saving procedures too dangerous to perform.

The continued spread of AMR genes threatens to unwind decades of medical progress. The problem affects all countries, but its impacts are often magnified in low- and middle-income nations where access to newer treatments is limited. Projections indicate that drug-resistant infections could cost the global economy trillions in lost output by 2050 if the trend is not reversed.