A Distinct Contractile Injection System Gene Cluster Found in a Majority of Healthy Adult Human Microbiomes

Abstract

Many commensal bacteria antagonize each other or their host by producing syringe-like secretion systems called contractile injection systems (CIS). Members of the Bacteroidales family have been shown to produce only one type of CIS—a contact-dependent type 6 secretion system that mediates bacterium-bacterium interactions. Here, we show that a second distinct cluster of genes from Bacteroidales bacteria from the human microbiome may encode yet-uncharacterized injection systems that we term Bacteroidales injection systems (BIS). We found that BIS genes are present in the gut microbiomes of 99% of individuals from the United States and Europe and that BIS genes are more prevalent in the gut microbiomes of healthy individuals than in those individuals suffering from inflammatory bowel disease. Gene clusters similar to that of the BIS mediate interactions between bacteria and diverse eukaryotes, like amoeba, insects, and tubeworms. Our findings highlight the ubiquity of the BIS gene cluster in the human gut and emphasize the relevance of the gut microbiome to the human host. These results warrant investigations into the structure and function of the BIS and how they might mediate interactions between Bacteroidales bacteria and the human host or microbiome. IMPORTANCE To engage with host cells, diverse pathogenic bacteria produce syringe-like structures called contractile injection systems (CIS). CIS are evolutionarily related to the contractile tails of bacteriophages and are specialized to puncture membranes, often delivering effectors to target cells. Although CIS are key for pathogens to cause disease, paradoxically, similar injection systems have been identified within healthy human microbiome bacteria. Here, we show that gene clusters encoding a predicted CIS, which we term Bacteroidales injection systems (BIS), are present in the microbiomes of nearly all adult humans tested from Western countries. BIS genes are enriched within human gut microbiomes and are expressed both in vitro and in vivo. Further, a greater abundance of BIS genes is present within healthy gut microbiomes than in those humans with with inflammatory bowel disease (IBD). Our discovery provides a potentially distinct means by which our microbiome interacts with the human host or its microbiome.

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

“…1b ) and Parabacteroidetes genera. Bacteroides was recently reported by the Shikuma group as being eCIS-rich 30 .

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Developmental staging and future research directions of the model marine tubewormHydroides elegans

“…The copyright holder for this preprint this version posted October 25, 2022. ; https://doi.org/10.1101/2022.10.24.513551 doi: bioRxiv preprint machinery Hydroides uses to sense these products could lead to broader discoveries about mechanisms and tools for host-microbe interactions. For example, we found that gene clusters encoding Contractile Injection Systems originally discovered to promote Hydroides metamorphosis are strikingly similar to gene clusters found in Bacteroidales bacteria from healthy human microbiomes 62 . Moreover, understanding the payload delivery and targeting mechanism of the MACs produced by P. luteoviolacea could enable us to produce new types of therapeutic delivery systems 63 .…”

Future research directions of the model marine tubeworm Hydroides elegans and synthesis of developmental staging of the complete life cycle

“…The products bacteria produce to promote Hydroides metamorphosis and the machinery Hydroides uses to sense these products could lead to broader discoveries about mechanisms and tools for host‐microbe interactions, and how these interactions evolve on a genetic and chemical level. For example, we found that gene clusters encoding Contractile Injection Systems originally discovered to promote Hydroides metamorphosis are strikingly similar to gene clusters found in Bacteroidales bacteria from healthy human microbiomes 59 . Moreover, understanding the payload delivery and targeting mechanism of the MACs produced by P. luteoviolacea could enable new types of therapeutic delivery systems 60 …”

“…For example, we found that gene clusters encoding Contractile Injection Systems originally discovered to promote Hydroides metamorphosis are strikingly similar to gene clusters found in Bacteroidales bacteria from healthy human microbiomes. 59 Moreover, understanding the payload delivery and targeting mechanism of the MACs produced by P. luteoviolacea could enable new types of therapeutic delivery systems. 60…”