Abstract

Type VI Secretion Systems (T6SSs) are widespread in bacteria and can dictate the development and organisation of polymicrobial ecosystems by mediating contact dependent killing. In Neisseria species, including Neisseria cinerea a commensal of the human respiratory tract, interbacterial contacts are mediated by Type four pili (Tfp) which promote formation of aggregates and govern the spatial dynamics of growing Neisseria microcolonies. Here, we show that N. cinerea expresses a plasmid-encoded T6SS that is active and can limit growth of related pathogens. We explored the impact of Tfp on N. cinerea T6SS-dependent killing within a colony and show that pilus expression by a prey strain enhances susceptibility to T6SS compared to a non-piliated prey, by preventing segregation from a T6SS-wielding attacker. Our findings have important implications for understanding how spatial constraints during contact-dependent antagonism can shape the evolution of microbial communities.

Highlights

  • The human microbiota is critical for the development of a healthy gastrointestinal immune system (Round and Mazmanian, 2009; Sommer and Backhed, 2013) and can protect the host from invasion by pathogenic bacteria (Kamada et al, 2013)

  • We identified a single locus in N. cinerea isolate CCUG346T (346T) that encodes homologues of all 13 components that are necessary for a functional T6SS (Cascales and Cambillau, 2012), including genes predicted to encode canonical T6SS components Hcp and VgrG (Figure 1A and Supplementary file 1)

  • We identified a T6SS in a commensal Neisseria spp. which can kill T6SS-deficient N. cinerea isolates and the related pathogens, N. meningitidis, with which it shares an ecological niche (Knapp and Hook, 1988), and N. gonorrhoeae

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Summary

Introduction

The human microbiota is critical for the development of a healthy gastrointestinal immune system (Round and Mazmanian, 2009; Sommer and Backhed, 2013) and can protect the host from invasion by pathogenic bacteria (Kamada et al, 2013). T6SS-associated effectors possess a broad range of activities, including nucleases (Koskiniemi et al, 2013; Ma et al, 2014; Pissaridou et al, 2018), phospholipases (Flaugnatti et al, 2016; Russell et al, 2013), peptidoglycan hydrolases (Whitney et al, 2013), and pore-forming proteins (Mariano et al, 2019); each effector is associated with a cognate immunity protein to prevent self-intoxication and to protect against kin cells (Alcoforado Diniz et al, 2015; Unterweger et al, 2014) In pathogens such as Pseudomonas, Vibrio, Salmonella, and Shigella, the impact of the T6SS in pathogenesis and bacterial competition has been established in vitro and in some cases in vivo (Anderson et al, 2017; Sana et al, 2016). Commensal bacteria harbour T6SSs, how these systems combat pathogens has only been elucidated for Bacteroidetes in the intestinal tract (Russell et al, 2014); further studies are needed to gain a greater

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