Hannah Ledvina Ph.D.
banner
hannahledvina.bsky.social
Hannah Ledvina Ph.D.
@hannahledvina.bsky.social
Incoming Assistant Professor of MCDB at the University of Michigan. Former JCCF and Leading Edge Postdoc Fellow in the Aaron Whiteley lab at CU Boulder. Predatory bacteria and phage enthusiast obsessed with host-pathogen interactions. She/her.
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!
July 2, 2025 at 8:10 PM
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!!
July 2, 2025 at 8:10 PM
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.
July 2, 2025 at 8:10 PM
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!
July 2, 2025 at 8:10 PM
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.
July 2, 2025 at 8:10 PM
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!
July 2, 2025 at 8:10 PM
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!
July 2, 2025 at 8:10 PM
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.
July 2, 2025 at 8:10 PM
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.
July 2, 2025 at 8:10 PM
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.
July 2, 2025 at 8:10 PM
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.
July 2, 2025 at 8:10 PM
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!
July 2, 2025 at 8:10 PM
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!
July 2, 2025 at 8:10 PM
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?
July 2, 2025 at 8:10 PM
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!
July 2, 2025 at 8:10 PM
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!
June 25, 2025 at 9:15 PM
The Ledvina lab will open its doors at the beginning of August! Stay tuned for updates!
June 25, 2025 at 9:10 PM
And endless thanks to the numerous people who have helped me along the way! There are truly too many to list here.
June 25, 2025 at 9:10 PM
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.
June 25, 2025 at 9:10 PM
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.
June 25, 2025 at 9:10 PM