MCR-1 findings in gulls show mobility of resistance threat

flying seagull
flying seagulls

Suwapitch Rimpongpisan/ Flickr cc

The feared antibiotic resistance factor MCR-1 has been found in seagulls in Argentina and Lithuania, raising the possibility that migratory birds may further spur the already global spread of the threat, according to two of a flurry of MCR-1 reports released this week.

Besides the seagulls, scientists have found MCR-1 in bacteria from hospital patients in Ecuador and Poland, sick chickens in China, and meat samples in Portugal, according to the new reports in the Journal of Antimicrobial Chemotherapy (JAC) and Epidemiology and Infection.

The reports underline once again the hitchhiking prowess of the MCR-1 resistance gene. Scientists say the gene, if it teams up with certain other resistance genes, could render bacteria resistant to all existing drugs.

MCR-1 confers resistance to colistin, a last-resort antibiotic for drug-resistant infections. The gene was first detected in China in November 2015, and since then at least 20 countries have reported it, according to the US Centers for Disease Control and Prevention (CDC). In the United States, MCR-1 was found in Escherichia coli from a Pennsylvania woman in May and also was found recently in stored E coli samples from two pigs.

Instead of being anchored to a bacterial chromosome, the MCR-1 gene is carried on a plasmid, a ring of DNA that can pass between different bacterial species. In most cases the gene has been found in E coli, but it also has been detected in Salmonella, Shigella sonnei, and Klebsiella pneumoniae.

Seagulls on two continents

In one of the JAC reports, Lithuanian researchers said they found the MCR-1 gene in E coli from 1 of 117 fecal and cloacal samples collected in January 2016 from European herring gulls that frequented a garbage dump in the city of Kaunas. They found that the isolate was resistant to ampicillin and ampicillin/sulbactam as well as colistin, but was susceptible to all other antibiotics tested.

They billed the discovery as the first known occurrence of the MCR-1 gene in E coli carried by a wild migratory bird, to the best of their knowledge. Gulls that were ringed in Lithuania have later turned up in nearly all European countries, showing the extent of their migrations, the researchers said.

They commented that inappropriate management of medical, biological, and food waste may contribute to the spread of infectious agents by wild birds, especially gulls, adding, "Water contaminated by faeces of birds should be foreseen as an important risk factor for transmission of resistant bacteria."

The other seagull find involved Kelp gulls in Argentina, according to European researchers writing in JAC. In surveillance in 2012 for bacteria with extended-spectrum cephalosporin resistance (ESCR), the team collected 50 fecal samples from Kelp gulls in Ushuaia, Argentina. Five E coli isolates from the samples showed colistin resistance, and the MCR-1 gene was detected in all five.

The discovery was the first detection of MCR-1 in Kelp gulls, as best they could determine. The authors also observed that MCR-1 has rarely been found in any wild animals, which don't naturally come into contact with antibiotics.

"The fact that gull species migrate, sometimes even between continents, indicates that they may play a role in the global dissemination of these clinically relevant bacteria," the authors said.

Surgery-related finding in Ecuador

In Ecuador, an E coli isolate from a 14-year-old boy who had an appendectomy was found to have the MCR-1 gene, marking its first appearance in the Andean region of South America, according to a report in Epidemiology and Infection.

The researchers, from two universities in Quito, said necrotic areas were found during the boy's appendectomy, so peritoneal fluid samples were taken and cultured. The samples yielded a colistin-resistant E coli isolate, and molecular analysis confirmed the presence of the MCR-1 gene. The isolate was susceptible to carbapenem, amikacin, and gentamicin but resistant to tigecycline, cirprofloxacin, and cephalosporins.

The isolate was identified as sequence type 609, a strain that was previously found in rooks in Poland, glaucous-winged gulls in Russia, dog feces in Denmark, and a patient in Canada, the authors said.

They judged that the strain was probably part of the boy's normal gut bacteria. It is suspected, they said, that the spread of MCR-1 bacteria is the result of the use of polymyxins, the drug class that includes colistin, in livestock, and polymyxins are approved for veterinary use and in food animals in Ecuador. The patient reported frequent trips to an intensive livestock production area, and those trips probably contributed to his exposure to the MCR-1 E coli strain, the researchers said.

MCR-1 in Polish patient

Possible exposure to livestock is also mentioned in a JAC report of MCR-1 in a Polish patient. Colistin-resistant E coli was found last October in the urine of a woman in her 50s who had pneumonia, diarrhea, and a urinary tract infection. She had no recent travel history, but she lived in a rural area, suggesting possible contact with livestock, the authors said.

Polymerase chain reaction (PCR) testing confirmed MCR-1 in the woman's isolate, and antimicrobial susceptibility testing showed that it was resistant to eight classes of antibiotics but susceptible to four, the report says.

It notes that Poland's national laboratory began surveillance for colistin-resistance in 2014. Of 37 Enterobacteriaceae isolates submitted for testing by the end of 2015, the woman's E coli isolate was the only MCR-1 producer.

"Even though fragmentary, the patient’s data correspond to the hypothesis that an agriculture associated MCR-1 reservoir exists," the researcher said, adding that MCR-1 is known to have been present in European livestock for more than 10 years.

"The isolate characteristics accord with the growing knowledge on E. coli as the major MCR-1 host and the high genetic diversity of MCR-1-positive isolates," they concluded.

MCR-1 and ESBL found together in chicken

In another JAC report, Chinese researchers said they found four MCR-1 producing Salmonella isolates from sick chickens. The detections resulted from a surveillance program for chicken Salmonella strains that carry another resistance factor, extended-spectrum beta lactamase (ESBL).

Under the program, 53 ESBL-positive Salmonella isolates were collected from diseased chickens in eight Chinese provinces in 2014 and 2015. Four of these were positive for MCR-1. In one isolate, a Salmonella enterica strain from Sichuan province, both MCR-1 and one type of ESBL gene, called blaCTX-M-55, were found on a single plasmid.

This find, together with other data from sequencing of the entire plasmid, "indicates that the genetic environment of the mcr-1 gene is more mobile than we expected," the authors said.

They said it appears that MCR-1 easily coexists with ESBL genes. "The coexistence of mcr-1 and blaCTX-M genes on a single plasmid presents more severe challenges in terms of controlling the election and transmission of mcr-1," they added.

"Strong evidence exists for the ongoing transmission of mcr-1 on a global scale and its co-occurrence on plasmids with blaCTX-M genes. This evidence is of gave concern and merits immediate action to limit the selection and transmission of mcr-1 in order to preserve the efficacy of polymyxins," the report concludes.

MCR-1 in retail meat samples

In Portugal, a survey of the antibiotic susceptibility of Salmonella in retail meat samples collected in 2011 and 2012 led to the detection of MCR-1, according to still another JAC report. Of 258 S enterica samples, 37 showed colistin resistance, and testing of these revealed that 4—all the Typhimurium serotype—were positive for MCR-1.

One of the isolates contained the ESBL factor CTX-M-1. The authors were able to identify the MCR-1-containing plasmids in two of the isolates but couldn’t identify those in the other two, an observation "that supports the diversity of genetic platforms of mcr-1 with the ability to disseminate," they wrote.

The geographic origins of the samples were unknown, and they might have included meat from various sources, the report says.

"It is obvious that mcr-1 is present in different plasmids and appears to have inserted into different genetic environments, factors that may impact its spread geographically," the researchers said. "Hence more genome data should be generated to fully understand the threat of a rapid widespread distribution. Nevertheless, our findings, and those of others, call for immediate action at an international level on the use of colistin in animal production."

See also:

Extract of Jun 20 JAC report on detection in herring gulls in Lithuania

Extract of Jun 20 JAC report on findings in Kelp gulls in Argentina

Jun 22 Epidemiology & Infection abstract on Ecuador case

Extract of Jun 20 JAC report on MCR-1 case in Poland

Extract of Jun 20 JAC report on MCR-1 in chickens in China

Extract of Jun 20 JAC report on MCR-1 in meat in Portugal

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