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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

I am extremely excited to continue determining the role of functional amyloids in the bacterial immune system and to keep using ExpND to identify new defensive systems in my future lab at the University of Michigan!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

This was truly a wild ride and I cannot thank the people involved enough! Shout out to @rsayegh.bsky.social who helped make the initial discoveries! A huge thank you to both @jcchildsfund.bsky.social and @leadingedgeprogram.bsky.social for their support! And of course @aaronwhiteley.bsky.social!!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

In total, we used a panel of wild E. coli strains to determine that functional amyloids protect against diverse predatory bacteria. These amyloids form a molecular suit-of-armor that protects the host cell from attack! We termed out approach 'ExpND' for exploring wild strains for novel defense.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

To determine if diverse functional amyloids in bacteria can defend against Bdello, we test the amyloid produced by Pseudomonas aeruginosa. Overexpression of this system in either E. coli of Pseudomonas resulted in reduced Bdello infection! So indeed this is a common features of these systems!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

Examples of diverse curli-like operons can be found throughout bacteria with all sorts of interesting accessory genes. Additionally, we (re)identified the functional amyloids of Pseudomonas which had been previously described to, like curli, play a role in biofilm formation.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

We next sought to better understand the distribution of these structures and teamed up with Aravind at the NIH to define the distribution of functional amyloids throughout bacteria. And what do you know, they are everywhere!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

Based on our model that curli acts like a suit-of-armor we hypothesized that it should also protect against other extracellular threats. We turned to another predatory bacteria, Myxococcus xanthus, which has a distinct lifecycle from Bdello. Amazingly curli also provides robust defense against Myxo!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

Amazed by this finding we next asked if curli was responsible for defense in all the resistant E. coli. Indeed we found this to be true for the majority of strains (stay tuned for more on this!) demonstrating that curli is widely used by E. coli for defense against Bdello.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

We found that resistant strains of E. coli completely coat their outer membrane in curli fibers, effectively acting as a molecular suit-of-armor against invading Bdello. Attached TEM: E coli, green; Bdello, orange; curli, purple.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

To better understand how curli is providing defense from Bdello we simply looked at the interaction between Bdello and a resistant host through TEM. Nothing could have prepared my for the incredible images we were about to see.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

Curli is primarily thought to play a role in biofilm formation as it helps stabilize the extracellular matrix. Curli is composed of the functional amyloid protein CsgA, which, just like the amyloids that cause neurodegeneration, form highly stable fibers.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

Here is where things got really interesting: transposon mutagenesis of one the resistant strains uncovered that production of the functional amyloid curli was responsible for defense against Bdello! Production of curli was both necessary and sufficient for defense demonstrating a new role curli!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

To ask this we decided to take a unique approach and screen wild bacteria for naturally resistant hosts. Amazingly this revealed that ~1/3 of E. coli strain are HIGHLY resistant to Bdello infection! This suggests that indeed, bacteria possess mechanisms to defend against predatory bacteria!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

Bdello is a predatory bacteria that invades into Gram-negative organisms. It is within this host that Bdello replicates with the lifecycle sharing many similarities with phage! And so we asked the question, how do host bacteria defend themselves from this threat?

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

This project started back in 2020 when I had first joined Aaron's lab and we were asking ourselves the question "do bacteria have immune pathways against things beyond phage"? This lead us to investigate my favorite organism Bdellovibrio bacteriovorus aka Bdello: a bacteria that eats other bacteria!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

Words cannot describe how excited I am to share the findings from the second half of my postdoc in @aaronwhiteley.bsky.social's lab where we discover that bacteria use functional amyloids to defend themselves from predatory bacteria. rdcu.be/euu5Y. See thread for details on this epic adventure 1/.

Functional amyloid proteins confer defence against predatory bacteria

Nature - Escherichia coli uses curli fibres, oligomers of the functional amyloid CsgA, as a barrier to protect against the predatory bacteria Bdellovibrio bacteriovorus and Myxococcus xanthus in a...

rdcu.be

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jun 25

I would also like to thank both @jcchildsfund.bsky.social and @leadingedgeprogram.bsky.social to believing in me when I was early in my postdoc training! These two incredible organization have provided me with incredible support and mentorship opportunities!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jun 25

The Ledvina lab will open its doors at the beginning of August! Stay tuned for updates!

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jun 25

And endless thanks to the numerous people who have helped me along the way! There are truly too many to list here.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jun 25

A monumental thank you to @aaronwhiteley.bsky.social for taking me on as a postdoc when the lab was still brand new. I have loved every minute of working together and exploring the bacterial immune system.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jun 25

I could have never gotten here without the endless support of my mentors, both formal and informal. A huge thank you to Joseph Mougous and members of his lab for helping me find my love for combining microbiology and biochemistry. I could have never asked for a better PhD experience.

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jun 25

Extremely excited to share I have accepted an offer to be an Assistant Professor in the MCDB department at the University of Michigan! Go Blue! The Ledvina lab will investigate the molecular interworking of the bacterial immune systems including defense against both viral and bacterial pathogens.

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Reposted by Hannah Ledvina Ph.D.

Sternberg Lab @sternberglab.bsky.social · Jun 11

1/10 New pre-print(s) from the Sternberg Lab in collaboration with Leifu Chang's Lab! We uncover the unprecedented molecular mechanism of CRISPR-Cas12f-like proteins, which drive RNA-guided transcription independently of canonical promoter motifs.
Full story here:
www.biorxiv.org/content/10.1...

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Reposted by Hannah Ledvina Ph.D.

Aaron Whiteley @aaronwhiteley.bsky.social · Apr 8

Check out our new story led by @aesully98.bsky.social describing how bacteria turn immune evasion against phage! In collaboration with @benmorehouse.bsky.social lab, we discover that bacteria guard their nucleotide second messenger pool using a nucleotidyltransferase related to Cas10/CRISPR enzymes

Ashley Sullivan @aesully98.bsky.social · Mar 31

Excited to share that my work from the @aaronwhiteley.bsky.social lab is now on bioRxiv! With @benmorehouse.bsky.social, we discovered that the Panoptes defense system—named after the all-seeing watchman of Hera—uses decoy nucleotides to detect phage anti-defense proteins.

A minimal CRISPR polymerase produces decoy cyclic nucleotides to detect phage anti-defense proteins

Bacteria use antiphage systems to combat phages, their ubiquitous competitors, and evolve new defenses through repeated reshuffling of basic functional units into novel reformulations. A common theme ...

www.biorxiv.org

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Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Apr 8

Stop your scrolling and read this AMAZING story from my coworker @aesully98.bsky.social in @aaronwhiteley.bsky.social's lab in collaboration with @benmorehouse.bsky.social ! An immune system which detects anti-immune mechanisms, incredible!!

Ashley Sullivan @aesully98.bsky.social · Mar 31

Excited to share that my work from the @aaronwhiteley.bsky.social lab is now on bioRxiv! With @benmorehouse.bsky.social, we discovered that the Panoptes defense system—named after the all-seeing watchman of Hera—uses decoy nucleotides to detect phage anti-defense proteins.

A minimal CRISPR polymerase produces decoy cyclic nucleotides to detect phage anti-defense proteins

Bacteria use antiphage systems to combat phages, their ubiquitous competitors, and evolve new defenses through repeated reshuffling of basic functional units into novel reformulations. A common theme ...

www.biorxiv.org

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