Genomic network analysis of environmental and livestock F-type plasmid populations

F-type plasmids are diverse, full of antibiotic resistance genes, and on the move! We investigated their population structure in a large sample of environmental Enterobacterales to understand what makes them tick.

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Why care about F-type plasmids?

The rivers, farms and wastewater around us act as reservoirs for antimicrobial resistance (AMR) [1], posing a significant risk to all areas of medicine. Resistance to many important antibiotics is on the rise, so it's of immediate clinical interest to understand how the genes conferring AMR are spread between reservoirs, in order to design effective interventions.

Horizontal gene transfer can accelerate the spread of AMR genes both within and across species. This is when AMR genes spread on mobile genetic elements such as plasmids. A major plasmid family involved in AMR gene spread are the so-called F-type plasmids, especially when it comes to extended-spectrum beta-lactamases (enzymes which break down beta-lactam antibiotics). In one study, almost 40% of plasmid-borne carbapenemases were on F-type plasmids [2]. Moreover, these F-type plasmids are often conjugative [3]: they can move between host bacteria, bringing their AMR genes along for the ride. Therefore, understanding F-type population structures is a step towards unpicking the AMR highway. However, these plasmids are very genomically diverse, which makes this difficult.

Community spirit

We chose to study F-type plasmids using genomic networks: structures which link together similar plasmids and separate dissimilar plasmids. We used plasmids found in bacteria sampled from livestock (cattle, pig and sheep) and from water environments. The latter included samples from the influent and effluent of wastewater treatment works, as well as upstream and downstream of the effluent. This allowed us to find natural groups of F-type plasmids which clumped together in our networks, known as communities.

We found that reservoir and the genus of the bacteria strongly shaped community membership. Communities often shared a unique backbone: a set of mutual core genes, almost like a postcode! This suggests that these communities of F-types can stably persist in the 
environment around us. Often, variation in the backbone was linked closely to the accessory genes present in the plasmid (genes not essential to F-type function, including AMR genes). You can think of this like the different styles of houses within a postcode, each adapted to its specific location. The association of F-type plasmids with AMR may reflect this ability to rapidly adapt to a niche.

Wider context

Genomic networks seem to be a good way to understand these environmental F-type plasmids, but this is just one aspect of the problem of AMR. As well as plasmids, other mobile genetic elements such as transposons are also responsible for moving AMR genes around. Combined with clonal spread, mutations, and other means, understanding the AMR network is a complex challenge.

This study formed part of the REHAB project, an interdisciplinary collaboration which explored the environmental resistome in a region of England in 2017. More information on the project is available here: https://modmedmicro.nsms.ox.ac.uk/rehab/

Our paper is available here: https://www.nature.com/articles/s41396-021-00926-w

Cover image created with https://biorender.com

References

[1] Woolhouse M, Ward M, van Bunnik B, Farrar J. Antimicrobial resistance in humans, livestock and the wider environment. Philos Trans R Soc Lond B Biol Sci. 2015;370(1670):20140083.

[2] Mbelle NM, Osei Sekyere J, Amoako DG, Maningi NE, Modipane L, Essack SY, et al. Genomic analysis of a multidrug‐resistant clinical Providencia rettgeri (PR002) strain with the novel integron ln1483 and an A/C plasmid replicon. Ann NY Acad Sci. 2020;1462(1):92–103.

[3] Rozwandowicz M, Brouwer MS, Fischer J, Wagenaar JA, Gonzalez-Zorn B, Guerra B, et al. Plasmids carrying antimicrobial resistance genes in Enterobacteriaceae. J Antimicrob Chemother. 2018;73(5):1121–37.

William Matlock

PhD Student, University of Oxford