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!

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!

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!

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.

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.

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!

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!

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?

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.

explore pathogen evasion mechanisms

 
Along the way we discuss strategies used to identify new defense systems

Next, we explore the similarities in immune signaling schemes and discuss how, even when the components vary, signaling pathways share common features.

Over the last several years the field of phage defense has taken off with the discovery of 100s of new systems

It’s here! Thrilled to be sharing a review article I wrote with @aaronwhiteley.bsky.social exploring the similarities and conservation of immune systems across life rdcu.be/dzSa3