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Reposted by Lingchong You

Bacterial Genomics @bactgenrss.bsky.social · Jul 2

Scaling laws of bacterial and archaeal plasmids www.nature.com/articles/s41...

Scaling laws of bacterial and archaeal plasmids - Nature Communications

The capacity of a plasmid to express genes is constrained by parameters such as its length and copy number. Here, Maddamsetti et al. present a computational method that enables rapid and accurate dete...

www.nature.com

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Reposted by Lingchong You

Jerónimo Rodríguez-Beltrán @jerorb.bsky.social · Jul 2

🚨🚨New paper out in @natcomms.nature.com!!

Come for the first large-scale analysis of plasmid copy number across species,
stay for one of the most intriguing results of my lab: universal scaling laws in plasmid biology! 📈🧬

👉 www.nature.com/articles/s41...

Universal rules govern plasmid copy number - Nature Communications

Plasmids exhibit a broad range of sizes and copies per cell, and these two parameters appear to be negatively correlated. Here, Ramiro-Martínez et al. analyse the copy number of thousands of diverse b...

www.nature.com

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Lingchong You @lingchongyou.bsky.social · Apr 11

12/ Congrats again to the team and particularly to Ryan, Hye-in and Grayson.

Lingchong You @lingchongyou.bsky.social · Apr 11

11/ After successfully eliminating the target plasmid, DoS safely self-destructs via induced self-cutting, leaving behind plasmid-free bacteria. This built-in containment ensures minimal ecological impact, maximizing safety and utility.

1

Lingchong You @lingchongyou.bsky.social · Apr 11

10/ Conceptually, DoS operates as a microbial gene drive. While gene drives have been widely explored in insect population control, our design demonstrates a novel application to bacterial plasmids.

1

Lingchong You @lingchongyou.bsky.social · Apr 11

9/ Once inside, DoS spreads efficiently by hijacking the target plasmid's own transfer machinery. It simultaneously outcompetes and suppresses the target plasmid through incompatibility and/or CRISPR-guided cutting.

1 1

Lingchong You @lingchongyou.bsky.social · Apr 11

8/ In mixed bacterial communities, self-transmissible plasmids transfer from their original hosts into cells carrying the DoS plasmid. This process exposes a critical vulnerability known as "retrotransfer." This allows DoS to infiltrate target-host populations.

1

Lingchong You @lingchongyou.bsky.social · Apr 11

7/ How does DoS work? It contains a transfer origin (oriT) but lacks its own transfer machinery, staying dormant unless interacting with bacteria that carry the targeted self-transmissible plasmid.

1

Lingchong You @lingchongyou.bsky.social · Apr 11

6/ We engineered a "denial-of-spread" (DoS) plasmid that acts as a Trojan horse, infiltrating and targeting bacterial populations harboring harmful conjugative plasmids.

1

Lingchong You @lingchongyou.bsky.social · Apr 11

5/ Traditional methods for plasmid curing, such as chemical agents, often lack specificity, inadvertently harming beneficial plasmids and disrupting microbial communities.

1

Lingchong You @lingchongyou.bsky.social · Apr 11

4/ Thus, proactive control of these mobile plasmids is critical for antibiotic stewardship efforts aimed at curbing the spread of resistance genes.

1

Lingchong You @lingchongyou.bsky.social · Apr 11

3/ Self-transmissible conjugative plasmids are major vectors spreading antimicrobial resistance (AMR). Their high mobility helps them persist even if they are costly to bacterial hosts.

1

Lingchong You @lingchongyou.bsky.social · Apr 11

2/ This was the final chapter of the dissertation work by Ryan Tsoi (now a Senior Scientist at Merck) and was carried through the finish line by Hye-in Son (now at BillionToOne) and @graysonshamrick.bsky.social

1

Lingchong You @lingchongyou.bsky.social · Apr 11

1/ What's the worst enemy of a plasmid? Another plasmid! Our new study demonstrates synthetic plasmids engineered as "Trojan horses" to eliminate plasmids encoding antibiotic resistance. @dukeubme.bsky.social www.science.org/doi/10.1126/...

A predatory gene drive for targeted control of self-transmissible plasmids

A biological “denial-of-spread” (DoS) strategy leverages retrotransfer to eliminate target plasmids in microbial communities.

www.science.org

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Lingchong You @lingchongyou.bsky.social · Apr 10

12/ Congrats again to the team and particularly to Ryan, Hye-in and Grayson.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

11/ After successfully eliminating the target plasmid, DoS safely self-destructs via induced self-cutting, leaving behind plasmid-free bacteria. This built-in containment ensures minimal ecological impact, maximizing safety and utility.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

10/ Conceptually, DoS operates as a microbial gene drive. While gene drives have been widely explored in insect population control, our design demonstrates a novel application to bacterial plasmids.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

9/ Once inside, DoS spreads efficiently by hijacking the target plasmid's own transfer machinery. It simultaneously outcompetes and suppresses the target plasmid through incompatibility and/or CRISPR-guided cutting.

1 1

Lingchong You @lingchongyou.bsky.social · Apr 10

8/ In mixed bacterial communities, self-transmissible plasmids transfer from their original hosts into cells carrying the DoS plasmid. This process exposes a critical vulnerability known as "retrotransfer." This allows DoS to infiltrate target-host populations.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

7/ How does DoS work? It contains a transfer origin (oriT) but lacks its own transfer machinery, staying dormant unless interacting with bacteria that carry the targeted self-transmissible plasmid.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

6/ We engineered a "denial-of-spread" (DoS) plasmid that acts as a Trojan horse, infiltrating and targeting bacterial populations harboring harmful conjugative plasmids.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

5/ Traditional methods for plasmid curing, such as chemical agents, often lack specificity, inadvertently harming beneficial plasmids and disrupting microbial communities.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

4/ Thus, proactive control of these mobile plasmids is critical for antibiotic stewardship efforts aimed at curbing the spread of resistance genes.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

3/ Self-transmissible conjugative plasmids are major vectors spreading antimicrobial resistance (AMR). Their high mobility helps them persist even if they are costly to bacterial hosts.

1

Lingchong You @lingchongyou.bsky.social · Apr 10

2/ This was the final chapter of the dissertation work by Ryan Tsoi (now a Senior Scientist at Merck) and was carried through the finish line by Hye-in Son (now at BillionToOne) and @graysonshamrick.bsky.social

1