Prospective Bacterial Genomic Surveillance

One of the things the evul federal gummint is gearing up to every food borne bacterial disease isolate that is sent to either the CDC or public health labs in what is known as the GenomeTrakr Network (I’ve heard this battle station project might be fully operational by 2018, though it’s already sequencing thousands of isolates per year).

With that background, this report from MMWR about the discovery of a colistin resistant E. coli food-borne isolate that has the transmissible mcr-1 gene is very interesting (boldface mine):

The mcr-1 gene confers resistance to the polymyxins, including the antibiotic colistin, a medication of last resort for multidrug-resistant infections. The mcr-1 gene was first reported in 2015 in food, animal, and patient isolates from China (1) and is notable for being the first plasmid-mediated colistin resistance mechanism to be identified. Plasmids can be transferred between bacteria, potentially spreading the resistance gene to other bacterial species. Since its discovery, the mcr-1 gene has been reported from Africa, Asia, Europe, South America, and North America (2,3), including the United States, where it has been identified in Escherichia coli isolated from three patients and from two intestinal samples from pigs (2,4–6). In July 2016, the Pathogen Detection System at the National Center for Biotechnology Information (Bethesda, Maryland) identified mcr-1 in the whole genome sequence of an E. coli isolate from a Connecticut patient (7); this is the fourth isolate from a U.S. patient to contain the mcr-1 gene.

The isolate was non-Shiga toxin–producing E. coli O157 from stool collected on June 16, 2016 from a pediatric patient with diarrhea. The patient traveled to the Caribbean for approximately 2 weeks to visit friends and relatives and developed fever and bloody diarrhea on June 12, 2 days before returning to the United States. The patient took paromomycin, an aminoglycoside antibiotic, from symptom onset until a pediatric outpatient visit on June 16, at which time a stool specimen was collected. The patient was not hospitalized and, in addition to the primary care visit, had one brief emergency department visit during the illness.

E. coli O157 harboring mcr-1 was isolated from three stool cultures from the patient: the June 16 culture and follow-up cultures on June 18 and 23. Reference susceptibility testing by broth microdilution showed that the isolates had a colistin (also known as polymyxin E) minimum inhibitory concentration (MIC) of 2 μg/ml, and polymyxin B MIC of 4 μg/ml. The isolates also carried a plasmid blacmy-2 gene, which encodes AmpC, an enzyme that confers resistance to third generation cephalosporins; the isolates were susceptible to carbapenems.

I don’t know if this is the first, but it’s certainly one of the first cases where, during routine surveillance, a genome sequence was used to identify a bacterial isolate with a clinically important phenotype (colistin resistance). Usually, it’s the other way around: known resistant organisms are sequenced to learn more about them. In this case, colistin resistance was identified ‘second-hand’–the GenomeTrakr Network uses genome sequencing to determine if two food-borne isolates might be part of an outbreak or if they’re independent events. But if you have a genome sequence, there’s a lot more that can be learned about an organism. Keep in mind that the patient was in the health system only long enough for a sample to be collected–this was not someone languishing in a hospital. In other words, it was an ‘ordinary’ food borne illness*. Without genome sequencing, we would have never known that this isolate carried mcr-1.

For a project like GenomeTrakr which collects thousands of isolates, phenotypic testing is very expensive–and for hospitals too–so the ability to identify ‘hidden’ resistance genes is a very promising development.

*In the U.S., certain food borne illness are required to be reported to state public health laboratories, including anything that might be E. coli O157:H7.

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