Bacterial death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans

Abstract

Several homologous domains are shared by eukaryotic immunity and programmed cell-death systems and poorly understood bacterial proteins. Recent studies show these to be components of a network of highly regulated systems connecting apoptotic processes to counter-invader immunity, in prokaryotes with a multicellular habit. However, the provenance of key adaptor domains, namely those of the Death-like and TRADD-N superfamilies, a quintessential feature of metazoan apoptotic systems, remained murky. Here, we use sensitive sequence analysis and comparative genomics methods to identify unambiguous bacterial homologs of the Death-like and TRADD-N superfamilies. We show the former to have arisen as part of a radiation of effector-associated α-helical adaptor domains that likely mediate homotypic interactions bringing together diverse effector and signaling domains in predicted bacterial apoptosis- and counter-invader systems. Similarly, we show that the TRADD-N domain defines a key, widespread signaling bridge that links effector deployment to invader-sensing in multicellular bacterial and metazoan counter-invader systems. TRADD-N domains are expanded in aggregating marine invertebrates and point to distinctive diversifying immune strategies probably directed both at RNA and retro- viruses and cellular pathogens that might infect such communities. These TRADD-N and Death-like domains helped identify several new bacterial and metazoan counter-invader systems featuring under-appreciated, common functional principles: the use of intracellular invader-sensing lectin-like (NPCBM and FGS), transcription elongation GreA/B-C, glycosyltransferase-4 family, inactive NTPase (serving as nucleic-acid-receptors) and invader-sensing GTPase switch domains. Finally, these findings point to the possibility of multicellular bacteria-stem metazoan symbiosis in the emergence of the immune/apoptotic systems of the latter.

Bacterial NLR-related proteins protect against phage

“…These can be further divided into 2 types: i. The FGS domain type -this has a single FGS domain that in several cases likely undergoes directed diversification by the DGR Reverse transcriptase (Kaur et al, 2020(Kaur et al, , 2021. Thus, they may be potential bacterial analogs of metazoan adaptive antigen-receptors like antibodies or TCRs.…”

“…"TM regions": These are typified by multiple TM regions (sometimes inserted into the NACHT module). A subset of bacterial NACHT proteins with this type of sensing domain likely recognize intra-membrane or periplasmic signals (Kaur et al, 2020(Kaur et al, , 2021. 5.…”

“…vi. Other potential protein-modifying enzymes (e.g., protein (S/T/Y) kinase, GT4 family glycosyltransferases) (Kaur et al, 2020(Kaur et al, , 2021). 2.…”

“…"Adaptors": These effectors without clear catalytic functions that may inhibit phage replication by recruiting other, endogenous host effectors or activating a transcriptional response. i. Effector Associated Domains and Death-like domains (Kaur et al, 2020(Kaur et al, , 2021 ii. Transcription regulatory/DNA-binding domains (e.g., wHTH domains) iii.…”

Immune Response of Eastern Honeybee Worker to Nosema ceranae Infection Revealed by Transcriptomic Investigation

“…Intriguingly, there was no DEG enriched in apoptosis in this work. Apoptosis plays a primary role in the growth and development of vertebrates and invertebrates [78]. This strategy is also employed by insects to fight against pathogens [79,80].…”