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https://www.science.org/content/blog-post/old-time-bacterial-plasmids-vs-modern-days

It’s been obvious for many years now that growing antibiotic resistance is a problem, and that it could turn into a very bad one. There has been a great deal of work put into trying to understand the nature of these resistance pathways, but if you’re studying bacterial pathogens in the modern world, you’re showing up at the crime scene long after the break-in.

You might be surprised to learn (I was!) that there is actually a resource of pathogenic bacteria from the pre-antibiotic era. The “Murray collection” has several hundred bacterial varieties in it, mostly from the Enterobacteriaceae and specifically a number of Escherichia, Shigella, Klebsiella, Salmonella, and Enterobacter species that were collected from 1917 to 1954 by Everitt George Dunne Murray during his long career. These were stored as cultures on agar slopes, and curation of this collection was continued by his son Robert Everitt George Murray during the mid-20th century. In the early 1980s, subcultures of all of these were transferred to the National Collection of Type Cultures in the UK, where they are still available today.

This is obviously a uniquely valuable resource, and the world of infectious disease biology is indebted to the Murrays (father and son) for what must have seemed at times like a very odd use of time and effort. Over the years there have been many studies of the Murray cultures, and a number of very interesting things have been discovered - for example, it was found a few years ago that the majority of the Klebsiella strains in the collection were resistant to penicillin before penicillin even came into any widespread use. They were already prepared with beta-lactamases, presumably due to the natural occurence of such antibiotics in soils and other locations.

Here’s a new paper studying the Murray strains, specifically looking at the DNA plasmids that these bacteria carry. Those are the unfortunately all-too-swappable elements that bacteria trade around, and are a primary method by which resistance spreads through a population. They find that the great majority of the Murray-ra plasmids aren’t carrying many resistance genes per se. About 23% of the old plasmids have actually never been seen again in bacterial sequence databases in the modern era, but there are some from all the way back to 1917 that are still around (in modified form) in 2020. What this team found was that modern bacterial pathogens are dominated by large plasmids that have incorporated the older ones in their sequences, with several lines of evidence suggesting that they’re the product of multiple fusion events over the years.

As mentioned, the early plasmids have low levels of resistance genes scattered among them, mostly efflux pumps and a few for dealing with cationic peptides. The modern plasmids. . .are not like that. 38% of them are carrying resistance genes, often multiple copies, conferring resistance to a whole range of agents, many of them the broad-spectrum or “last resort” antibiotics, oh joy. The peak are plasmids that carry up to 40 different resistance genes, spanning a dozen different antibiotic types.

The authors were able to see several broad types of plasmid in the modern samples, and it appears that those behemoth polyresistance modern plasmids are probably short-ilved, with a lot of the nasty diversity lurking in smaller, more stable and persistent sequences that are mixes of old-fashioned Murray sequences (and their descendants) with modern resistance genes. But as they authors note, it’s not just the presence of resistance genes that determines that fate of all these bacterial plasmids - there are clearly evolutionary forces at work beyond just those from antibiotics, and those need to be better understood. The bacteria are nowhere near giving up all their secrets.

https://www.science.org/content/blog-post/old-time-bacterial-plasmids-vs-modern-days