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Retaining the resistance: MCR-1, colistin + lysozyme
If you’ve been following the news about antibiotic resistant bacteria, you may have heard about a particularly alarming plasmid: MCR-1. A plasmid is a circle of DNA that is relatively small and mobile – an easy way for genetic information to spread between bacteria. MCR-1 raises concern because it provides bacteria resistance against the last-resort antibiotic colistin. The CDC reports MCR-1 was found in both patients and livestock in the United States this summer.
David Weiss, director of Emory’s Antibiotic Resistance Center, and colleagues have a short letter in The Lancet Infectious Diseases showing that MCR-1 also confers resistance to an antimicrobial enzyme produced by our bodies called lysozyme. MCR-1-containing strains were 5 to 20 times less susceptible to lysozyme, they report.
This suggests that the pressure of fighting the host immune system may select for MCR-1 to stick around, even in the absence of colistin use, the authors say.
While the findings are straightforward in bacterial culture, Weiss cautions that there is not yet evidence showing that this mechanism occurs in live hosts. For those that really want to get alarmed, he also calls attention to a recent Nature Microbiology paper describing a hybrid plasmid with both MCR-1 and resistance to carbapenem, another antibiotic.
Islet transplants from fish?
The shortage of human organ donors has led scientists to investigate animals as a potential source for transplantable organs or tissues. Pigs are often mentioned because of their size: similar to ours.
Recently, prospects for xenotransplantation brightened when Harvard geneticist George Church demonstrated the removal of dozens of endogenous retroviruses from the pig genome, in a tour de force of the CRISPR/Cas9 gene editing technique.
Emory researchers Susan Safley and Collin Weber have been exploring the possibility of using different animals for xenotransplantation: fish, specifically tilapia.
Why fish? This review details several advantages tilapia may offer in the field of islet transplant, but first â€“ a reminder about islets.
Islets are the clusters of cells in the pancreas that produce insulin. Several clinical trials, including this one led by Emoryâ€™s Nicole Turgeon, have shown that islets isolated from deceased human donors can restore normal blood sugar regulation in patients with type 1 diabetes. Still, obstacles remain such as the shortage of human islets, and the loss of insulin independence over time, even with the use of drugs that hold off immune rejection.
For islet transplant, here are some of the proposed advantages presented by tilapia:
*tilapia have large, distinct islet organs called Brockmann bodies that are easy to isolate
*tilapia grow quickly and cost less to raise than pigs
*tilapia islets are resistant to hypoxia, thought to contribute to graft loss
*tilapia do not express alpha (1,3) gal, a carbohydrate structure present on mammalian cells that causes hyperacute rejection Read more
Regenerative Engineering & Medicine highlights
Last week on Friday, Lab Land attended the annual Regenerative Engineering & Medicine center get-together to hear about progress in this exciting area.
During his talk, Tony Kim of Georgia Tech mentioned a topic that Rose Eveleth recently explored in The Atlantic: why arenâ€™t doctors using amazing â€œnanorobotsâ€ yet? Or as Kim put it, citing a recent review, â€œSo many papers and so few drugs.â€
[A summary: scaling up is difficult, testing pharmacokinetics, toxicity and efficacy is difficult, and so is satisfying the FDA.]
TheÂ talks Friday emerged from REM seed grants; manyÂ paired an Emory medical researcher with a Georgia Tech biomedical engineer. All of these projects take on challenges in delivering regenerative therapies: getting cells or engineered particles to the right place in the body.
For example, cardiologist W. Robert Taylor discussed the hurdles his team had encountered in scaling up his cells-in-capsules therapies for cardiovascular diseases to pigs, in collaboration with Luke Brewster. The pre-pig phase of this research is discussed in more detail here and here. Read more