Environmental Sensing in Actinobacteria: a Comprehensive Survey on the Signaling Capacity of This Phylum

Abstract

Signal transduction is an essential process that allows bacteria to sense their complex and ever-changing environment and adapt accordingly. Three distinct major types of signal-transducing proteins (STPs) can be distinguished: one-component systems (1CSs), two-component systems (2CSs), and extracytoplasmic-function factors (ECFs). Since Actinobacteria are particularly rich in STPs, we comprehensively investigated the abundance and diversity of STPs encoded in 119 actinobacterial genomes, based on the data stored in the Microbial Signal Transduction (MiST) database. Overall, we observed an approximately linear correlation between the genome size and the total number of encoded STPs. About half of all membrane-anchored 1CSs are protein kinases. For both 1CSs and 2CSs, a detailed analysis of the domain architectures identified novel proteins that are found only in actinobacterial genomes. Many actinobacterial genomes are particularly enriched for ECFs. As a result of this study, almost 500 previously unclassified ECFs could be classified into 18 new ECF groups. This comprehensive survey demonstrates that actinobacterial genomes encode previously unknown STPs, which may represent new mechanisms of signal transduction and regulation. This information not only expands our knowledge of the diversity of bacterial signal transduction but also provides clear and testable hypotheses about their mechanisms, which can serve as starting points for experimental studies. IMPORTANCEIn the wake of the genomic era, with its enormous increase in the amount of available sequence information, the challenge has now shifted toward making sense and use of this treasure chest. Such analyses are a prerequisite to provide meaningful information that can help guide subsequent experimental efforts, such as mechanistic studies on novel signaling strategies. This work provides a comprehensive analysis of signal transduction proteins from 119 actinobacterial genomes. We identify, classify, and describe numerous novel and conserved signaling devices. Hence, our work serves as an important resource for any researcher interested in signal transduction of this important bacterial phylum, which contains organisms of ecological, biotechnological, and medical relevance. Bacterial survival critically depends on the ability to swiftly respond to environmental changes. To efficiently monitor the surrounding environment, microbial genomes encode numerous and highly diverse proteins that can sense a given extracellular stimulus, transmit the signal to the cytoplasm, and elicit a proper response. These signal-transducing proteins (STPs) can be divided into three major groups: one-component systems (1CSs), two-component systems (2CSs), and extracytoplasmic-function factors (ECFs). The vast majority of STPs in bacteria are 1CSs. These systems are composed of a single protein that contains an input domain, which senses the stimulus, and an output domain, which elicits the response by binding nucleic acids, modifying proteins, or performing an enzymati...

Themes and variations in gene regulation by extracytoplasmic function (ECF) sigma factors

“…The ECF sigma factor family now comprises approximately 38 000 genes from 7679 bacterial genomes and constitutes one of the major signal transduction systems in bacteria [12 •• ,13]. Phylogenetic analyses have defined 56 major and 32 minor ECF sigma factor families based on sequence similarity and genomic context [12 •• ,13,14].…”

“…Phylogenetic analyses have defined 56 major and 32 minor ECF sigma factor families based on sequence similarity and genomic context [12 •• ,13,14]. Predicted and confirmed ECF sigma factors and their family affiliation, where known, can be found in the Microbial Signal Transduction (MiST2) database (http://mistdb.com/).…”

“…Predicted and confirmed ECF sigma factors and their family affiliation, where known, can be found in the Microbial Signal Transduction (MiST2) database (http://mistdb.com/). Most bacteria possess multiple ECF sigma factors, the number of which is roughly correlated with the size of the genome and the lifestyle of the organism [12 •• ,13]. In general, bacteria with large genomes, complex developmental programs, and that live in niches subject to fluctuating environmental conditions have larger numbers of ECF sigma factors, whereas species with smaller genomes that inhabit relatively stable environments have few or no ECF sigma factors.…”

“…This domain consists of a three-helix bundle and is followed by a fourth helix whose position varies (Figure 2) [28]. Currently, bioinformatic analyses that combine structural and sequence information have identified ASD-like domains in genes co-transcribed with ECF sigma factors for approximately 50% of the ECF families [12 •• ,13,26]. The majority of these proteins are predicted to be single-pass transmembrane proteins with the ASD in the N-terminal cytoplasmic domain [13].…”

“…The majority of these proteins are predicted to be single-pass transmembrane proteins with the ASD in the N-terminal cytoplasmic domain [13]. The periplasmic domains of the predicted anti-sigma factors vary considerably among different ECF families suggesting that they have diverged to recognize disparate signals [12 •• ,13]. …”