NLM DIR Seminar Schedule

Abstract:

Bacterial warfare is a widespread phenomenon in which bacteria deploy toxins to inhibit or kill competitors. These toxins disrupt essential cellular processes, and their diversification is driven by an evolutionary arms race involving toxin and immunity gene acquisition. Here, we used in silico approaches to analyze genomes from the 10kSalmonella Project and identify effectors secreted via the Type VI Secretion System (T6SS). We uncovered 128 candidates distributed across diverse Salmonella serovars and other bacterial species, including a protein harboring a previously unknown circularly permuted variant of NlpC/P60 clade of the papain-like fold.

Strikingly, conflict-associated versions of the permuted NlpC/P60 scaffold arose at distinct points in its evolutionary history and now function in different biological conflict systems. Here, we investigate two such cases. The first, from Salmonella, acts as a T6SS effector mediating interbacterial competition. The second, identified in Legionella, is associated with the Type IV Secretion System (T4SS) and contributes to virulence in eukaryotic hosts. In both instances, comparative evolutionary analyses strongly implicated lipids as primary targets, and experimental validation by collaborating laboratories respectively confirmed their phospholipase and S-palmitoyl transferase activities. Together, these findings reveal how a conserved catalytic scaffold has been repeatedly repurposed to mediate distinct forms of antagonism, from bacterial competition to host–pathogen interactions