Antimicrobial Peptides, Polymorphic Toxins, and Self-Nonself Recognition Systems in Archaea: an Untapped Armory for Intermicrobial Conflicts

Abstract

Numerous, diverse, highly variable defense and offense genetic systems are encoded in most bacterial genomes and are involved in various forms of conflict among competing microbes or their eukaryotic hosts. Here we focus on the offense and self-versus-nonself discrimination systems encoded by archaeal genomes that so far have remained largely uncharacterized and unannotated. Specifically, we analyze archaeal genomic loci encoding polymorphic and related toxin systems and ribosomally synthesized antimicrobial peptides. Using sensitive methods for sequence comparison and the “guilt by association” approach, we identified such systems in 141 archaeal genomes. These toxins can be classified into four major groups based on the structure of the components involved in the toxin delivery. The toxin domains are often shared between and within each system. We revisit halocin families and substantially expand the halocin C8 family, which was identified in diverse archaeal genomes and also certain bacteria. Finally, we employ features of protein sequences and genomic locus organization characteristic of archaeocins and polymorphic toxins to identify candidates for analogous but not necessarily homologous systems among uncharacterized protein families. This work confidently predicts that more than 1,600 archaeal proteins, currently annotated as “hypothetical” in public databases, are components of conflict and self-versus-nonself discrimination systems. IMPORTANCE Diverse and highly variable systems involved in biological conflicts and self-versus-nonself discrimination are ubiquitous in bacteria but much less studied in archaea. We performed comprehensive comparative genomic analyses of the archaeal systems that share components with analogous bacterial systems and propose an approach to identify new systems that could be involved in these functions. We predict polymorphic toxin systems in 141 archaeal genomes and identify new, archaea-specific toxin and immunity protein families. These systems are widely represented in archaea and are predicted to play major roles in interactions between species and in intermicrobial conflicts. This work is expected to stimulate experimental research to advance the understanding of poorly characterized major aspects of archaeal biology.

The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins

“…It contains the Zn-binding mo f HExxH which characterizes many metalloproteases [32][33][34][35] . This domain, previously termed PVC-metallopep dase, was iden fied as a marker of eCIS based on limited genome analyses 36,37 but its role has never been studied in a broad and func onal context. By analyzing the eCIS operons and proteins we iden fied that DUF4157 is strongly associated with a high number of puta ve eCIS toxins, either as a gene that is adjacent to toxins or in the form of a mul domain protein, in which DUF4157 is found at the N-terminus and the toxin domain is found at the C-terminus ( Figure S6).…”

Suicidal Leishmania

“…Toxins and AMPs are natural substances of both prokaryotic and eukaryotic origin [25,26]. Their role is generally related to offensive/defensive responses, resulting in damage or death of the targeted organism [27,28].…”

Overview of Global Trends in Classification, Methods of Preparation and Application of Bacteriocins

“…TP-A0584, also has a narrow spectrum of action, which is limited to members of the genus. The mechanism of action of LAPs has not been studied [ 38 ].…”