Antibiotic resistance is a significant challenge in modern medicine. A concerning development is the appearance of the MCR-1 gene, which allows bacteria to withstand a class of potent antibiotics used as a last resort. Its discovery signaled a new chapter in bacterial resistance because the gene can be transferred between different types of bacteria. This mobility makes it a subject of intense scientific scrutiny.
The Significance of Colistin Resistance
Colistin is a polymyxin antibiotic that was not a preferred treatment for decades due to its potential toxicity to the kidneys and nervous system. As safer alternatives were developed, its use was largely abandoned. This relegated colistin to the status of a “last-resort” antibiotic.
Its use is reserved for treating severe infections caused by multidrug-resistant bacteria that do not respond to other antibiotics. These are often life-threatening infections in hospital settings affecting critically ill patients. The bacteria responsible, like certain strains of Acinetobacter baumannii and Pseudomonas aeruginosa, have developed resistance to nearly all other drugs, making colistin the only viable treatment option.
The reintroduction of colistin into clinical practice highlights the severity of the antibiotic resistance crisis. Physicians must weigh the drug’s side effects against the risk of an untreatable infection. The emergence of resistance to this last line of defense is a concerning development, raising the possibility of infections that are untreatable with current medical technologies.
Mechanism of the MCR-1 Gene
Colistin’s effectiveness is based on its ability to disrupt the outer membrane of certain types of bacteria. It specifically targets a component of this membrane called Lipid A. Colistin molecules are positively charged and are attracted to the negatively charged Lipid A, binding to it and causing the membrane to become unstable and break down, which ultimately kills the bacterium.
The MCR-1 gene interferes with this process by producing an enzyme called phosphoethanolamine transferase. This enzyme modifies the structure of Lipid A by adding a phosphoethanolamine molecule to it. This addition alters the overall electrical charge of the Lipid A, making it less negative. As a result, the positively charged colistin is no longer strongly attracted to its target on the bacterial surface.
This modification effectively camouflages the bacterial membrane from the antibiotic. It is similar to changing the lock on a door so that the original key no longer fits. The antibiotic is still present, but it cannot bind to its target to carry out its function. This single biochemical change is sufficient to render the bacteria resistant to colistin’s effects.
Plasmid-Mediated Spread
The rapid spread of the MCR-1 gene is a primary reason for concern. The gene is located on a plasmid, a small, circular piece of DNA separate from the main bacterial chromosome. Plasmids can replicate independently and are mobile. This allows them to be transferred from one bacterium to another through a process called horizontal gene transfer.
This method of transmission is different from vertical gene transfer, where genetic information is passed from a parent cell to its offspring during cell division. Horizontal gene transfer allows for the exchange of genetic material between individual bacteria, even those that are not related or are of different species. For example, the MCR-1 gene can move from a relatively harmless E. coli to a more dangerous bacterium like Klebsiella pneumoniae.
Because the MCR-1 gene is on a plasmid, it can be copied and shared among a bacterial population with alarming speed. This contrasts with resistance from a random mutation in the main chromosome, which spreads much more slowly as bacteria reproduce. The mobility of plasmids allows a single resistance gene to quickly disseminate through diverse bacterial communities.
Global Impact and Detection
The MCR-1 gene was first identified by scientists in China in 2015 during routine surveillance in agricultural settings. It was found in E. coli samples from pigs, and shortly after this discovery, the same gene was found in human patients. The link between agricultural use and human infections became an immediate focus for researchers.
Since its initial identification, the MCR-1 gene has been detected in a wide range of bacteria across numerous countries. It has been found in various hosts, including pigs, poultry, and humans, as well as in food products like raw meat. The gene’s presence has been confirmed in bacteria like E. coli, Salmonella, and Klebsiella pneumoniae, demonstrating its ability to spread across species.
The gene’s presence in both livestock and humans suggests that agricultural practices, like using colistin to promote growth in animals, likely contributed to its emergence and spread. This has led to increased surveillance and calls for more restricted use of last-resort antibiotics in both medicine and agriculture. The goal is to mitigate the further dissemination of this resistance mechanism.