Researchers have identified a second sample of E. coli in human sample in the U.S. containing the mcr-1 gene. This comes nearly six weeks after the first case of a 49-year-old woman from Pennsylvania with a urinary tract infection caused by E. coli was found carrying the gene, mcr-1.  Mcr-1 is resistant to the antibiotic colistin, the last available effective drug that works against strains that have acquired protection against all other medications.  The results were published on July 11, 2016 by a team led by Mariana Castanheira from JMI Laboratories, North Liberty, Iowa, U.S. in the journal Antimicrobial Agents and Chemotherapy.

Meanwhile, in another study, which was also published on July 11, 2016 in the journal Antimicrobial Agents and Chemotherapy, a team of researchers led by Gian Maria Rossolini from the Università di Firenze, Florence, Italy found a variant of the mcr-1 gene.  The variant was found in Klebsiella pneumoniae and has been called mcr-1.2 gene.

Let us see what the discovery of a second case of mcr-1 gene in the U.S means before discussing the significance of the mcr-1 gene variant discovered by Dr. Firenze. E. coli with mcr-1 gene was found in 19 isolates collected from Belgium, Brazil, Germany, Hong Kong, Italy, Malaysia, Poland, Russia, Spain and the U.S.

During 2014-2015, nearly 21,000 samples of E. coli and K. pneumoniae were collected from 183 hospitals located in Asia-Pacific, Europe, Latin America and North America as part of the SENTRY Antimicrobial Surveillance Program.

Of these, 390 samples displayed resistance to colistin drug. Among the 390 E. coli and K. pneumoniae samples resistant to colistin, only 19 samples were positive for mcr-1 gene and were collected from 10 countries (Belgium, Brazil, Germany, Hong Kong, Italy, Malaysia, Poland, Russia, Spain and the U.S). All the 19 that tested positive for mcr-1 were in E. coli isolates, while all K. pneumoniae isolates tested negative for mcr-1.

While only one E. coli sample each tested positive for mcr-1 from seven countries, Italy had four E. coli strains positive for mcr-1, Germany had five and Spain had three.

The isolates were associated with bloodstream infections, skin and skin structure infections, urinary tract infections, respiratory tract infections, and intra-abdominal infections. The U.S. isolate came from a hospital in New York and was collected in May 2015.

The good news is that in contrast to the first case of E. coli with mcr-1 gene discovered in the U.S., the one found now is “susceptible to several antimicrobial agents”. But it is found to be resistant to ciprofloxacin, levofloxacin and a few other drugs. Overall, colistin-resistant mcr-1 positive isolates were carbapenem susceptible, they say. So the situation has not yet become grave.

A key question the authors are currently working to answer is whether the mcr-1 gene is plasmid-mediated in the isolates they have identified. Plasmid-mediated mcr-1 was first isolated from food animals and humans in China, in late 2015.

But there is every possibility of mcr-1 gene making certain microbes that are currently treated only by last-resort antibiotics become resistant.  This is because in the case of mcr-1, a small piece of DNA (plasmid) found outside the chromosome carries a gene responsible for antibiotic resistance. Since the gene is found outside the chromosome, it can spread easily between different types of bacteria, between patients as well as within a community.  Unlike the relatively long time taken for bacteria to be resistant to antibiotics, mcr-1 can induce resistance almost overnight.

The chances of a mobile gene encoding resistance to colistin evolving among isolates that are resistant to last-resort antibiotics would be a threatening proposition for treating serious infections.

A new variant

The novel mcr variant, named mcr-1.2, was found in K. pneumoniae from a rectal swab taken from a child suffering from leukemia in Italy.

The mcr-1.2 gene was carried on a plasmid that is different from mcr-1 plasmid but whose structure is very similar to that of mcr-1-bearing plasmids previously found in E. coli from different parts of the world.

While mcr-1 gene has mostly been found in E. coli isolates and never in K. pneumoniae strains (clonal group 258) which are mainly responsible for global-scale spread of KPC-type carbapenemases, the new variant was detected in KPC-producing K. pneumoniae strain, the authors write.

This is the first time that an mcr-type gene has been found to be associated with KPC-producing K. pneumoniae ST512, a strain of the bacteria that is resistant to carbapenems.

Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are a group of emerging highly drug-resistant bacilli causing infections associated with significant morbidity and mortality. The outbreak of KPC-producing bacteria was once confined to the U.S. but has now spread across the world.