The mcr-1 gene represents a concern in the global fight against antibiotic resistance. This gene provides bacteria with resistance to colistin, a last-resort antibiotic for severe infections. Its discovery has raised alarms, as it could undermine one of the few remaining effective treatments for highly resistant bacterial strains. The presence of mcr-1 poses a direct threat to public health by increasing the possibility of untreatable bacterial infections.
The Significance of Colistin Resistance
Colistin is a last-resort antibiotic, reserved for situations where other treatments have failed. It is primarily used to combat infections caused by multidrug-resistant Gram-negative bacteria, such as Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. These bacteria can cause serious health issues, including pneumonia, bloodstream infections, and complicated urinary tract infections. Colistin’s importance has grown as resistance to other broad-spectrum antibiotics, like carbapenems, has become more common.
The Mechanism of the MCR-1 Gene
The mcr-1 gene enables bacteria to resist colistin by encoding an enzyme called phosphoethanolamine transferase. This enzyme acts on the outer membrane of Gram-negative bacteria, modifying lipid A, a component of the lipopolysaccharide (LPS). The modification involves adding a phosphoethanolamine (pEtN) molecule to lipid A, which reduces the negative charge of the bacterial cell surface. Colistin typically binds to these negatively charged sites on the bacterial membrane, disrupting its integrity and leading to cell death. However, the mcr-1 modification significantly reduces colistin’s ability to bind to the altered lipid A, rendering the antibiotic ineffective by preventing its interaction with the bacterial cell.
How MCR-1 Spreads Between Bacteria
The mcr-1 gene’s ability to spread rapidly among different bacteria stems from its location on a mobile piece of DNA called a plasmid. Plasmids are small, circular DNA molecules that exist independently of a bacterium’s main chromosome. Unlike chromosomal genes, which are passed down vertically from parent to daughter cells, plasmids can be easily transferred horizontally between bacteria, even across different bacterial species. This process, known as horizontal gene transfer, often occurs through conjugation, where bacteria directly exchange genetic material.
The gene’s presence on plasmids allows it to disseminate efficiently within bacterial populations. This mobility means that a bacterium acquiring the mcr-1 gene can then pass this resistance trait to other susceptible bacteria it encounters, potentially leading to widespread resistance. Rapid transfer mechanisms contribute to the challenge of controlling antibiotic-resistant infections.
Global Spread and Public Health Impact
The mcr-1 gene was first identified in Escherichia coli from pigs in China in November 2015. Its emergence was linked to the extensive use of colistin in agriculture, particularly as a growth promoter in livestock feed. Following this discovery, mcr-1 was widely detected in human patients, food products, and environmental samples globally.
The public health impact of mcr-1 is the emergence of bacterial infections that are difficult to treat. Physicians face a challenge when confronted with infections caused by bacteria carrying mcr-1, especially if these bacteria are already resistant to multiple other antibiotics. This situation could lead to untreatable infections, resulting in higher rates of treatment failure, prolonged hospital stays, and increased mortality. The global spread of mcr-1 has underscored the interconnectedness of human, animal, and environmental health, often referred to as the “One Health” framework. This has prompted global surveillance efforts and calls for more stringent antibiotic stewardship programs in both human medicine and agricultural practices to preserve the effectiveness of colistin and other antibiotics.