Federal Scientists Find in U.S. Samples the MCR-1 Gene Responsible for Colistin Resistance

In November 2015, scientists from China reported the first instance of a gene that confers resistance to colistin, known as mcr-1. Colistin is an older antibiotic that is effective against certain hard-to-treat bacterial infections in humans. Since the discovery in China, a global search ensued for the mcr-1 gene, and it has also been reported in Europe and Canada.

Federal scientists have been searching for the mcr-1 gene in ill people, in retail meats, and in food animals since reports of its presence in other countries and have now discovered two instances of the mcr-1 gene that confers colistin resistance in the United States: one in a sample from a food animal and one in a sample from a patient. No evidence has been found linking these two findings.  These are the first isolates found in a search that began in 2015 and includes examination of approximately 55 ,000 isolates by federal scientists. The finding of mcr-1 in a human isolate was announced Tuesday, May 24, 2016, by the Department of Defense.

These findings are important because the mcr-1 gene is found on a plasmid, a small piece of DNA that can easily move from one bacterium to another, spreading resistant DNA between bacterial species.

The mcr-1 gene is also important because of the role colistin plays in human medicine. Colistin is commonly used in other parts of the world in human and animal medicine. In the United States, colistin is not used to treat animals but is used as a last-resort drug to treat patients with multi-drug resistant infections caused by CRE, “the nightmare bacteria.” Any gene that confers resistance to a drug of last resort is of public health concern.

One of the ways that scientists at the Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA), and the U.S. Department of Agriculture (USDA) have been searching for the mcr-1 gene is through the National Antimicrobial Resistance Monitoring System (NARMS), which has detected emerging resistance to clinically important antibiotics for the past 20 years. NARMS is a partnership among CDC, FDA and USDA, as well as state and local public health departments.

As a part of the NARMS effort, USDA’s Agricultural Research Service (ARS) scientists looked for the gene in intestinal samples from food animals: turkey, chicken, swine and cattle. A single strain of colistin-resistant E. coli was found in a pig intestinal sample, and a DNA sequence revealed that the strain contained the mcr-1 gene on a plasmid. To date, 949 animal samples in the ARS study have been screened; researchers plan to screen 2,000. The scientists also determined that the mcr-1 carrying colistin-resistant E. coli is resistant to other antibiotics including ampicillin, streptomycin, sulfisoxazole, and tetracycline.

CDC and FDA searched for the gene in the genome sequences of Enterobacteriaceae (Salmonella, Shigella/E. coli and Klebsiella) from human and retail meat sources. As of April 2016, about 54,000 isolates [including carbapenem-resistant Enterobacteriaceae (CRE)] from CDC, FDA, and the NCBI genomic database have been analyzed and none have shown the presence of the mcr-1 gene.

Although our findings suggest that mcr-1-mediated colistin resistance might be rare, CDC, FDA and USDA remind consumers that cooking all meat, poultry and fish to its proper internal temperature kills bacteria, viruses and other foodborne pathogens, whether or not they are antibiotic-resistant.

CDC reminds healthcare providers of the importance of preventing infections wherever healthcare is delivered and improving antibiotic use. CDC reiterates the need for a coordinated approach to prevent spread of antibiotic-resistant bacteria between patients and facilities, including CRE that potentially contains mobile plasmids such as mcr-1.

The NARMS partners will continue to study the newly isolated E. coli strain to better understand the mcr-1 gene. The findings could help determine additional steps to better understand the mechanisms and dissemination of mcr-1 and associated genes.

Beginning in fall 2016, CDC’s Antibiotic Resistance lab network will provide the infrastructure and lab capacity for seven to eight regional labs, and labs in all states and seven major cities/territories, to detect and respond to resistant organisms, including CRE recovered from human samples . State labs will be able to detect new forms of antibiotic resistance—including mutations that allow bacteria to survive the effects of the last-resort drugs like colistin—and report these findings to CDC in near real-time. With this comprehensive lab capacity, state health labs and regional labs that are part of the network will be able to investigate emerging resistance in ways currently unavailable, generating better data for stronger infection control among patients to prevent and combat future resistance threats.

And consistent with the National Action Plan for Combating Antibiotic Resistant Bacteria, CDC, FDA, USDA, DOD and other government agencies will continue efforts to track, slow and respond to the emergence of antibiotic resistance.

Antibiotic/Antimicrobial Resistance, CDC