1. What does resistance to colistin antibiotic mean?
Colistin resistance means that bacteria are resistant to colistin antibiotic. Colistin resistance may be the resultof changes in the chromosome of the bacteria, in other words, the more permanent part of its genome, or it may occur due to genes located outside the chromosome, in the additional genetic elements of bacterial genome called plasmids.
2. What is plasmid-mediated, transferable colistin resistance, and why is it considered more significant than the resistance genes in the bacterial chromosome?
Transferable colistin resistance refers to the colistin resistance genes found in the plasmids of bacteria. Plasmids can be transferred between different bacteria, which means that the resistance gene may also be transferred from one bacterial species to another. This makes it possible for the resistance to be transferred from a bacterial species that is harmless to humans to one that causes diseases. In contrast, the genes in the chromosome are only inherited by the daughter cells when bacteria multiply, but they are not transferred between bacteria in the same way as the genes in plasmids.
3. When was transferable colistin resistance discovered for the first time?
In November 2015, the respected medical journal Lancet published an article reporting the first discovery of the plasmid-mediated colistin resistance gene mcr-1 in China (Liu et al., 2015). This is a new, important discovery of a mechanism that allows colistin resistance to be transferred from one bacterium to another.
4. Where else has transferable colistin resistance been found?
After the Chinese article, the resistance gene mcr-1 has been found in animals and food around the world (Shen et al., 2016); for example, it was found in Denmark in meat of foreign origin (Hasman et al., 2015). In Europe, strains of Escherichia coli with the mcr-1 gene have been found in production animals in France, Germany and Belgium, among other countries (Skov & Monnet, 2016). Since then, several new transferable colistin resistance genes or their variations have been discovered (mcr-2, mcr-3, etc.) (Kluytmans et al. 2017). In a few cases fromlivestock and meat, the mcr-1 gene has also been found from the chromosome of E. coli (Veldman et al., 2016; Zurfluh et al., 2016; Donà et al., 2017). However, usually it is located in a plasmid.
5. Are colistin-resistant bacteria also resistant to other antibiotics?
Colistin-resistant bacteria may also be resistant to other antibiotics. Several publications have reported finding ESBL and mcr genes, among others, in the same strains of bacteria (Skov & Monnet, 2016). However, colistin resistance in bacteria can also occur without resistance to other antibiotics.
6. How does an animal get bacteria with colistin resistance?
The resistance may come from the animals' medication, the food they eat, or other animals.
7. Are the resistant bacteria in animals a threat to human health?
Transferable colistin resistance becoming increasingly common is considered to be a very great concern globally, because colistin is a so-called reserve antibiotic, meaning that it is used to treat human infections when other antibiotics are no longer effective. The most serious consequence of colistin resistance discovered in animals is the resistance being transferred from animals to humans. For example, the high incidence of ESBL in rescue dogs imported from abroad, combined with the discovery of colistin resistance, poses a clear threat to the health of the humans and animals that come into contact with these animals.
8. How is colistin resistance studied in Finland?
In Finland, the FINRES-Vet programme, which monitors the antimicrobial susceptibility of bacteria isolated from animals and food, colistin resistance has been studied since 2010 in E. coli, used as indicator bacteria. No resistance to colistin has been found in E. coli. Colistin resistance has also been studied in salmonella since early 2014. Some salmonella serotypes, such as S. Enteritidis, are naturally slightly less susceptible to colistin, but the exact mechanism is unknown. Such strains of salmonella have also been isolated in Finland, but the mcr-1 gene has not been detected in them.
9. How is colistin used?
Colistin is a critically important antibiotic in human medicine, and it is often the last option for treating severe infections caused by multidrug-resistant, gram-negative bacteria.
10. Is colistin used in Finland to treat animals?
Colistin is not used for production animals in Finland, but it is used in veterinary medicine in many other countries.
11. How long does colistin-resistant bacteria remain in the intestines of dogs?
There is no existing research on the subject at the moment.
Hasman, H, Hammerum, A.M., Hansen, F., Hendriksen, R.S., Olesen, B., Agers, Ø. .Y, Zankar,i E., Leekitcharoenphon, P., Stegger ,M., Kaas, R.S., Cavaco, L.M., Hansen, D.S., Aarestrup, F.M. & Skov, R.L. (2015): Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015. Euro Surveillance 2015.
Kluytmans (2017): Plasmid-encoded colistin resistance: mcr-one, two, three and counting. Euro Surveill. 2017.
Liu, Y.Y., Wang, Y., Walsh, T.R. et al. : Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study. Lancet Infect Dis. 2015.
Shen, Z., Wang, Y., Shen, Y., Shen, J. & Wu, C. (2016): Early emergence of mcr-1 in Escherichia coli from food-producing animals. Lancet Infect Dis, 16:161 - 168.
Skov, R.L. & Monnet D.L. (2016): Plasmid-mediated colistin resistance (mcr-1 gene): three months later, the story unfolds. Euro surveillance 2016.
Veldman, K., van Essen-Zandbergen, A., Rapallini, M., Wit, B., Heymans, R., van Pelt, W. & Mevius, D. (2016): Location of colistin resistance gene mcr-1 in Enterobacteriaceae from livestock and meat. Journal of Antimicrobial Chemotherapy.
Zurfluh, K., Tasara, T., Poirel, L., Nordmann, P. & Stephan, R. (2016): Draft genome sequence of Escherichia coli S51, a chicken isolate harbouring a chromosomally encoded mcr-1 gene. Genome Announcements, 4:4.