National Center for Emerging and Zoonotic Infectious Diseases
Emerging Resistance Updates: Plasmid-mediated
colistin resistance (mcr-1 gene)
LCDR Alison Laufer Halpin, PhD
Lead, Metagenomics and Molecular Biology Team
Clinical and Environmental Laboratory Branch
Division of Healthcare Quality Promotion, CDC
HICPAC Meeting
July 15, 2016
Plasmid-mediated colistin resistance (mcr-1 gene)
 First reported in November 20151
 Subsequent reviews of collections2
– mcr-1 gene undetected since 1980s
– Species
• Escherichia coli
• Klebsiella pneumoniae
• Salmonella enterica (multiple serotypes)
• Shigella sonnei
– Multiple plasmids
1. Liu YY et al. Lancet Infect Dis. 2016; 16(2):161-8.
2. Skov RL, Monnet DL. Euro Surveil. 2016; 21(9)
Plasmid-mediated colistin resistance (mcr-1 gene)
 Subsequent reviews of collections1
– Found globally
– Isolated from
• Food animals
• Environment
• Meat, vegetables
• Ill patients
• Asymptomatically colonized
1.
Skov RL, Monnet DL. Euro Surveil. 2016; 21(9)
mcr-1 gene in the United States
 May 2016: Department of Defense (DoD) reported E. coli with mcr-1 gene
 CDC working with DoD, state and local health departments
– Screen epidemiologically linked contacts
• Identify asymptomatically colonized people
• Household contacts, healthcare providers
• No positives
– Next-generation sequencing tools to sequence isolate
 Additional reports
– NY resident (2015)
– USDA and HHS search revealed 2 porcine E. coli isolates carrying mcr-1
DHQP Clinical and Environmental Microbiology Branch
 Conventional PCR to detect mcr-1 gene described in literature
 Developed TaqMan probe-based real-time PCR assay
 Advantages of real-time PCR
– No post-PCR processing required
– More precise
– Quantitative
TaqMan Probe-based Real-Time PCR Assay
 Optimized: 98% efficiency
 Validated
– 25 isolates, included 4 mcr-1 +
 Undergoing final review for CLIA
approval
Figure courtesy Jonathan Daniels, DHQP/CEMB
TaqMan Probe-based Real-Time PCR Assay
 Screen collections to search for mcr-1 gene
– Surveillance (2011-2016)
– Reference (January 2015)
 Colistin MIC>4 μg/mL
 All negative
 **Other mechanisms can confer resistance to colistin**
Whole Genome Sequence Data
 Screened our collection using mcr-1 sequence
 735 isolates with sequence data available
 Human isolates
– 690 Enterobacteriaceae
– 45 non-Enterobacteriaceae
 mcr-1
– 100% identity
– 10% identity
 No matches
mcr-2 in Belgium
 July 2016: Report of mcr-2
gene from porcine, bovine1
– ~76% nt identity to mcr-1
– ~80% protein identity
 Unsure how our mcr-1 assay
will perform
– mcr-2 real-time PCR assay
1. Xavier BB, et al. Eurosurveillance. 7 July 2016; 21(27)
Whole Genome Sequence Data
 Screened our collection using mcr-2 sequence
 735 isolates with sequence data available
 Human isolates
– 690 Enterobacteriaceae
– 45 non-Enterobacteriaceae
 mcr-2
– 100% identity
– 10% identity
 No matches
Thank you
For more information, contact CDC
1-800-CDC-INFO (232-4636)
TTY: 1-888-232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the
official position of the Centers for Disease Control and Prevention.