Antibiotic resistance is a significant global health challenge, threatening the effectiveness of modern medicine. Bacteria evolve mechanisms to evade antibiotics, making common infections difficult to treat. The emergence of the mobilized colistin resistance gene, `mcr-1`, in 2015 raised alarm among public health experts. This gene represents a concerning development in preserving effective treatments for bacterial pathogens.
Understanding the mcr-1 Gene
The `mcr-1` gene provides bacteria with resistance to colistin, a last-resort antibiotic for severe multidrug-resistant Gram-negative infections. Colistin, also known as polymyxin E, is reserved for cases where other antibiotics have failed. The `mcr-1` gene encodes phosphatidylethanolamine transferase. This enzyme modifies lipid A, a component of the bacterial outer membrane, by adding a phosphoethanolamine group. This alteration reduces colistin’s binding affinity, neutralizing its action and allowing bacteria to survive.
The `mcr-1` gene’s location on a plasmid distinguishes it from previous colistin resistance. Plasmids are small, circular DNA pieces that exist independently of the bacterial chromosome and transfer easily between bacteria. This allows `mcr-1` to spread among diverse bacterial species. The gene was first identified in China in 2015 in Escherichia coli from animals and human patients. Since its discovery, various `mcr` gene variants (from `mcr-1` to `mcr-10`) have been identified globally.
Pathways of mcr-1 Dissemination
The `mcr-1` gene primarily spreads through horizontal gene transfer, with plasmids as its main vehicle. This mechanism allows bacteria to share genetic material, including resistance genes, across different species. `mcr-1` can transfer between common bacteria in humans, animals, and the environment, such as Escherichia coli, Salmonella, and Klebsiella pneumoniae. Its ability to “jump” between different plasmids further enhances its transmissibility.
Widespread colistin use in agriculture, particularly in livestock like pigs in China, contributed to `mcr-1`’s emergence. From agricultural settings, `mcr-1` has disseminated globally through various routes. The movement of food animals and contaminated meat across international borders is a significant pathway. Human travel also contributes to its global distribution, as individuals can carry resistant bacteria. The gene can also enter the environment through wastewater and agricultural runoff, persisting in soil and water, potentially transferring to other bacterial populations.
Public Health Implications of mcr-1
The `mcr-1` gene presents a substantial threat to global public health, as colistin is a last-resort treatment for severe, drug-resistant bacterial infections. Resistance to this antibiotic can lead to a lack of effective treatment options. A major concern is `mcr-1` combining with other resistance genes already present in bacteria. Some bacteria may carry genes providing resistance to carbapenems, another class of last-resort antibiotics.
When `mcr-1` co-occurs with other resistance genes on the same mobile genetic element, it can lead to pan-drug resistant bacteria, often called “superbugs.” These superbugs are resistant to nearly all available antibiotics, rendering infections untreatable. Untreatable infections result in prolonged illness, increased hospital stays, and a higher risk of morbidity and mortality. This raises the specter of a “pre-antibiotic era,” where common bacterial infections could become deadly. `mcr-1` detection in human patients, even without international travel history, underscores its widespread dissemination and urgent public health implications.
Strategies for Containment
To mitigate the spread and impact of the `mcr-1` gene, a multifaceted approach involves enhanced surveillance, responsible antibiotic use, and international cooperation. Continuous monitoring of `mcr-1` in humans, animals, food, and the environment is crucial for tracking its spread and identifying outbreaks. This surveillance helps inform targeted interventions and public health responses.
Promoting antibiotic stewardship focuses on the responsible use of antibiotics in human and veterinary medicine. This includes reducing unnecessary prescriptions, ensuring appropriate dosing, and limiting colistin use in animal agriculture. Strict infection prevention and control measures in healthcare settings, farms, and communities curb the transmission of resistant bacteria. International collaboration among governments, health organizations, and researchers is essential for sharing data, coordinating surveillance efforts, and developing harmonized policies to combat this global threat.