A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria

Abstract

The Firmicutes are a phylum of bacteria that dominate numerous polymicrobial habitats of importance to human health and industry. Although these communities are often densely colonized, a broadly distributed contact-dependent mechanism of interbacterial antagonism utilized by Firmicutes has not been elucidated. Here we show that proteins belonging to the LXG polymorphic toxin family present in Streptococcus intermedius mediate cell contact- and Esx secretion pathway-dependent growth inhibition of diverse Firmicute species. The structure of one such toxin revealed a previously unobserved protein fold that we demonstrate directs the degradation of a uniquely bacterial molecule required for cell wall biosynthesis, lipid II. Consistent with our functional data linking LXG toxins to interbacterial interactions in S. intermedius, we show that LXG genes are prevalent in the human gut microbiome, a polymicrobial community dominated by Firmicutes. We speculate that interbacterial antagonism mediated by LXG toxins plays a critical role in shaping Firmicute-rich bacterial communities.DOI: http://dx.doi.org/10.7554/eLife.26938.001

Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system

“…To further explore the potential diversity of NADase effectors, we next used iterative homology search algorithms and identified two phylogenetically distinct families of T6SS NADases. One of these families also contains a significant number of proteins associated with the bacterial type VII secretion system (T7SS), a pathway recently implicated in interbacterial antagonism between Gram-positive bacteria (25,26). Taken together, our findings reveal a broad distribution of interbacterial NADase enzymes and provide insight into how a plant commensal bacterium inhibits the growth of its bacterial competitors.…”

“…Within this subset of proteins, we noted that 43 contain predicted LXG or WXG-100 domains at their N termini. LXG and WXG-100 proteins are substrates of the T7SS, and we and others have recently implicated this pathway in interbacterial antagonism among Gram-positive Firmicutes (25,26). Thus, it appears that NAD(P) ϩ -hydrolyzing enzymes mediate bacterial competition via multiple specialized protein secretion systems found in diverse bacterial phyla (Fig.…”

“…WXG-100 domains are established signal sequences for the T7SS and LXG domains, given their predicted structural similarity to WXG-100 domains, and likely also fulfill this role (37,38). Our recent characterization of T7SS-exported LXG substrates from Streptococcus intermedius B196 identified the TelB protein as an interbacterial NADase secreted by this organism (25). TelB bears no homology to the Tne1 or Tne2 families of NADases; rather, it belongs to a previously defined family of host celltargeting NADases.…”

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

“…are thought to occupy a crowded niche proximal to the gut mucosa and our findings herein provide evidence of extensive cell–cell contacts between species of the genus (Whitaker et al, 2017). The T6SS is one of many antagonistic pathways whose operation is determined by the presence or absence of polymorphic toxins and corresponding antitoxins (Aoki et al, 2010; Whitney et al, 2017; Zhang et al, 2012). Thus, our study offers an analytical framework for more globally deciphering the forces that dictate the establishment and maintenance of bacterial communities.…”

Expanding the molecular weaponry of bacterial species

“…Bacteria employ a variety of secretory mechanisms to mediate interbacterial interactions. Contact-dependent antagonistic interactions among Gram-negative bacteria are mediated by the T6SS 2 (2), whereas the T7SS is thought to be involved in those occurring among Gram-positive Firmicutes (3,4). In either case, the breadth of molecules mediating interbacterial killing remains only partially characterized.…”