Will Smith
@willpjsmith.bsky.social
280 followers 650 following 46 posts
I love science! I study toxin interactions in microbes. Dad of two @wellcometrust Sir Henry Wellcome Fellow | All views my own | he/him | 🏳️‍🌈
Posts Media Videos Starter Packs
willpjsmith.bsky.social
LOL wet! I don't think it's stopped raining for the last 24h ^^
willpjsmith.bsky.social
YES! Amazing news, big congrats Rachel! 🎉
Reposted by Will Smith
soreklab.bsky.social
Phage "satellites" that produce capsids but have no genes to produce tails have puzzled scientists for a long time. These are abundant as prophages in bacteria, but it was unclear how they can infect without tails

Now, Penadés & co show that they hijack tails from other phages. Incredible!
Reposted by Will Smith
joshuasweitz.bsky.social
New preprint bubbling up in our group for a while:

"Phase separation and coexistence in spatial coordination games between microbes"

www.biorxiv.org/content/10.1...

Generalizes findings of phase separation in microbes using T6SSs to a broad range of interaction mechanisms.

Li + Steinbach et al.
FIG. 3: Time lapse visualizations of a two player coordination game with payo matrix A = [10 5; 510]. The images show the spatial con guration (lattice size L = 256) at t = 0246810 with dt = 005. White corresponds to player 1 and black is player 2. Starting from well mixed initial condition, initial fraction of player 1 is 05, the two players separate into domains whose characteristic length scales (patch size) grow over time.
willpjsmith.bsky.social
Thanks for reading this thread! We hope the paper is interesting and useful Huge thanks to my coauthor @prokaryota.bsky.social for a really cool and enjoyable collab, Elisa is the best :-)

16/16
willpjsmith.bsky.social
If your lab does competition assays where microbial antagonism is (or may be!) involved, it might be worth doing a ground-truth check for biases like these. Also, some assays won't be affected e.g. if you use colorimetric killing assays that don't rely on a selection step or c.f.u. counting.

15/n
willpjsmith.bsky.social
What's our take-away? Competitive interactions are very common (see e.g. www.science.org/doi/10.1126/...) and we've shown they can be hard to quench in a killing assay. This can lead to over-estimation of strong competitive interactions.

14/n
Bacterial species rarely work together
Competition is prevalent and could be harnessed as an alternative to antibiotics
www.science.org
willpjsmith.bsky.social
Conversely, when Susceptible cells are rare (e.g. if they *didn't* do well in the competition assay), few dilutions are required to count Susceptible c.f.u.s. and there will be proportionally more contact with T6SS-armed Attackers. More T6SS contact, more residual killing, fewer c.f.u.s.

13/n
willpjsmith.bsky.social
When Susceptible cells are abundant (e.g. if they did pretty well in the competition assay), large dilutions are necessary to count c.f.u.s. These dilutions will tend to separate Attackers and Susceptibles and minimise residual killing on the selective media.

12/n
willpjsmith.bsky.social
Why does this bias results most where the Attacker : Susceptible ratio is high?

Here's a little cartoon explainer:

11/n
willpjsmith.bsky.social
We also found that, if cell mixtures are pre-incubated in a liquid antibiotic that selects against T6SS attackers, this reduces the bias, especially for longer pre-incubation times.

10/n
willpjsmith.bsky.social
We found that there was a strong, T6SS-dependent reduction in the number of E. coli c.f.u.s recovered, compared with the “”ground truth” densities we knew we should be getting (plotted here as a pink zone). The deviation tended to increase with increasing Attacker / Susceptible ratio.

9/n
willpjsmith.bsky.social
We wondered how this would bias the results of a killing assay. We devised a "ground-truth" experiment where we mixed E. coli and A. baylyi in known ratios, before diluting and plating on selective media as per a regular killing assay, to see what c.f.u. counts we'd get back.

8/n
willpjsmith.bsky.social
In other words, Kanamycin really isn’t quenching T6SS antagonism effectively in the aftermath of a killing assay, and so you’d predict that you’d get fewer E. coli CFUs as a result.

7/n
willpjsmith.bsky.social
We found that T6SS-armed A. baylyi ADP1 bacteria (often used to study T6SSs), will transiently still fire their T6SS harpoons under lethal selective conditions. Here we see ADP1 killing some green E. coli when ADP1 is supposed to be dead!

6/n
willpjsmith.bsky.social
Thinking about this in our own studies, we did some tests. Turns out that some antagonistic interactions, like those via harpoon-like Type 6 Secretion Systems (T6SSs), DON’T STOP just because cells are being selected against by lethal concentrations of antibiotic.

5/n
willpjsmith.bsky.social
The problem is this: if one population is antagonising another, how do you STOP that antagonism happening when you plate cells on selective media? After all, biology doesn’t stop for our convenience!

4/n
willpjsmith.bsky.social
Survival is then a read-out of competitive interactions: the lower the survival when populations are mixed c.f. control, the stronger the antagonism between them. Survival is often measured using c.f.u. counts on selective media.

3/n
willpjsmith.bsky.social
Some background: competition assays are common in microbiology. You mix different populations of microbes (normally 2 types for simplicity), allow them to compete, and then measure how many cells survive from each population, compared with some control where the populations don’t interact.

2/n
Reposted by Will Smith
royalsociety.org
The Royal Society David Attenborough Award and Lecture 2025 is awarded to Dr Roger Highfield for a vast contribution to public engagement, reaching audiences of millions through journalism, broadcast, books and museum-led initiatives. https://royalsociety.org/medals-and-prizes/attenborough-prize/
Reposted by Will Smith
proftracypalmer.bsky.social
Check out our latest preprint! We show that the same antibacterial toxin requires different immunity proteins depending whether it’s intra or extracellular
biorxiv-microbiol.bsky.social
Distinct immunity protein families mediate compartment-specificneutralisation of a bacterial toxin https://www.biorxiv.org/content/10.1101/2025.05.31.657152v1
willpjsmith.bsky.social
‪Well done @magdalenakurteu.bsky.social,
@matthewjshepherd.bsky.social,
@bexlowrypalms.bsky.social,
@flanagella.bsky.social‬,
Eric Chapman, Joy Hawley, Hannah Jones, Jeremy DeJardin and Logan Sauers!
willpjsmith.bsky.social
Go Team! Deeply honoured that the MERMan lab reps won an @manchester.ac.uk‬ "FMBH heroes" award - thanks ‪@fbmh-uom.bsky.social‬ and @mermanchester.bsky.social for nominating us ❤️❤️❤️