The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals Its Role in Community Composition

Abstract

Summary Although gut microbiome composition is well defined, the mechanisms underlying community assembly remain poorly understood. Bacteroidales possess three genetic architectures (GA1–3) of the type VI secretion system (T6SS), an effector delivery pathway that mediates interbacterial competition. Here we define the distribution and role of GA1–3 in the human gut using metagenomic analysis. We find that adult microbiomes harbor limited effector and cognate immunity genes, suggesting selection for compatibility at the species (GA1, GA2) and strain (GA3) levels. Bacteroides fragilis GA3 is known to mediate potent inter-strain competition, and we observe GA3 enrichment among strains colonizing infant microbiomes, suggesting competition early in life. Additionally, GA3 is associated with increased Bacteroides abundance, indicating that this system confers an advantage in Bacteroides-rich ecosystems. Collectively, these analyses uncover the prevalence of T6SS-dependent competition and reveal its potential role in shaping human gut microbial composition.

Bifunctional Immunity Proteins Protect Bacteria against FtsZ-Targeting ADP-Ribosylating Toxins

“…These include the Esx pathway, prevalent in the phyla Firmicutes and Actinobacteria, and the type VI secretion system (T6SS), which is widespread in the phyla Proteobacteria and Bacteroidetes. Pathogenic bacteria may use these pathways to facilitate invasion of or dominance within polymicrobial infections, whereas for commensal organisms they can dictate compatibility within consortia (Sana et al, 2016; Speare et al, 2018; Verster et al, 2017). …”

Causalities of war: The connection between type VI secretion system and microbiota

“…The role of GA1 and GA2 is unknown, but putative effector-immunity pairs (e.g., several evolved PAAR proteins with putative nuclease domains) hint at it being involved in interbacterial competition (Coyne et al, 2016). Supporting this notion, multiple species encode the same effector genes within a single microbiome (Verster et al, 2017). GA1 and GA2 are shared amongst Bacteroides (Coyne et al, 2016;Coyne et al, 2014), whereas GA3 is exclusively found in some Bacteroides fragilis strains (Coyne et al, 2014).…”

“…An analysis of infant microbiomes containing B. fragilis is significantly more likely to harbour GA3 structural genes (92%) compared with those of adults (74%), suggesting that GA3 mediates strain level competition early on in gut microbiota development (Verster et al, 2017). As Grampositive bacteria have not been shown to be targets of the T6SS, the decreased abundance of these genera in GA3-containing microbiomes is most likely due to a fitness advantage conferred to GA3 + B. fragilis and not direct action against Firmicutes (Verster et al, 2017). As Grampositive bacteria have not been shown to be targets of the T6SS, the decreased abundance of these genera in GA3-containing microbiomes is most likely due to a fitness advantage conferred to GA3 + B. fragilis and not direct action against Firmicutes (Verster et al, 2017).…”

Here, there, and everywhere: How pathogenicEscherichia colisense and respond to gastrointestinal biogeography

“…Type VI secretion systems (T6SSs), likened to molecular crossbows, are used to transfer toxic effector proteins into target cells and are prevalent within Gram‐negative bacteria including both commensals and AE pathogens. For example, commensal Bacteroidales use T6SSs for competition within the infant microbiome, which has a significant impact on community formation and structure (Verster et al, ). Importantly, enteric pathogens use T6SSs to counteract colonisation resistance by the microbiota.…”

“…Bacteroidales use T6SSs for competition within the infant microbiome, which has a significant impact on community formation and structure (Verster et al, 2017). Importantly, enteric pathogens use T6SSs to counteract colonisation resistance by the microbiota.…”