An RNA-centric view on gut Bacteroidetes

Abstract

Bacteria employ noncoding RNAs to maintain cellular physiology, adapt global gene expression to fluctuating environments, sense nutrients, coordinate their interaction with companion microbes and host cells, and protect themselves against bacteriophages. While bacterial RNA research has made fundamental contributions to biomedicine and biotechnology, the bulk of our knowledge of RNA biology stems from the study of a handful of aerobic model species. In comparison, RNA research is lagging in many medically relevant obligate anaerobic species, in particular the numerous commensal bacteria comprising our gut microbiota. This review presents a guide to RNA-based regulatory mechanisms in the phylum Bacteroidetes, focusing on the most abundant bacterial genus in the human gut, Bacteroides spp. This includes recent case reports on riboswitches, an mRNA leader, and cis- and transencoded small RNAs (sRNAs) in Bacteroides spp. and a survey of CRISPR-Cas systems across Bacteroidetes. Recent work from our laboratory now suggests the existence of hundreds of noncoding RNA candidates in Bacteroides thetaiotaomicron, the emerging model organism for functional microbiota research. Based on these collective observations, we predict mechanistic and functional commonalities and differences between Bacteroides sRNAs and those of other model bacteria, and outline open questions and tools needed to boost Bacteroidetes RNA research.

Paraphocaeicola brunensis gen. nov., sp. nov., Carrying Two Variants of nimB Resistance Gene from Bacteroides fragilis, and Caecibacteroides pullorum gen. nov., sp. nov., Two Novel Genera Isolated from Chicken Caeca

“…So far, only little is known about CRISPR-Cas systems among members of the family Bacteroidaceae , in particular about their function within gut microbiota and effect on HGT. The genus Bacteroides seems to be typical with the presence of CRISPR-Cas type II system, unlike the rest of the Bacteroidetes members ( 24 ). However, studies on B. fragilis isolates showed presence of three different CRISPR-Cas systems resembling type IB, type IIIB, and type IIC systems, which seem to be associated with different virulences of these strains ( 25 ).…”

Comparative genomics provides structural and functional insights into Bacteroides RNA biology

“…Bacterial species of the Proteobacterium phylum—including the genuses Escherichia and Salmonella —have long served us as model Gram‐negative organisms including for RNA research (Hör et al, 2020). In stark contrast, RNA biology is poorly understood in the distantly related genus Bacteroides (Figure 1a) (Ryan et al, 2020b). Given the profound impact global RBPs exert on proteobacterial sRNA function, we first performed an in silico search for Bacteroides proteins harboring known RNA‐binding domains using Pfam release 32 (El‐Gebali et al, 2019).…”

“…coli and Salmonella enterica (Hör et al, 2020; Sharma & Vogel, 2009). However, these methods have not yet been widely transferred to obligate anaerobic bacteria (Ryan et al, 2020b), hampering the functional and mechanistic study of sRNAs in many medically relevant gut microbiota species. In parallel to establishing comparable experimental tools, computational methods offer a fast‐track solution to uncover sRNA functions in those species.…”

“…Mapping and functionally analyzing this “RNA microbiome” bears great potential to uncover novel functions and mechanisms employed by bacterial RNA molecules and the proteins they interact with. While experimental toolkits are being developed to study RNA‐related processes in different representatives of the microbiota (Fuchs et al, 2021; Ponath et al, 2021; Ryan et al, 2020b), informatic approaches, such as comparative genomics, offer an entry point to explore RNAs expressed by human microbiotas (Fremin & Bhatt, 2021; Weinberg et al, 2010). In the present study, we have leveraged in silico tools and combined them with experimental approaches to improve our understanding of the RNA biology of the gut microbiota member B .…”

“…protect their host from enteric infections by priming the development of the immune system and providing colonization resistance against pathogens (Buffie & Pamer, 2013; Hooper et al, 2000). In contrast to the situation in the model organisms of the Proteobacteria, Bacteroidetes RNA research is only in its infancy (Ryan et al, 2020b). For example, in contrast to other Gram‐negative phyla where sRNA function is often tied to assisting RNA chaperones such as Hfq (Kavita et al, 2018) or FinO domain‐containing proteins such as ProQ (Olejniczak & Storz, 2017), no global RBP is known in Bacteroidetes, though RRM‐domain‐containing proteins have recently been suggested as candidates (Adams et al, 2021).…”