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 Streptococus 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.
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Funding
Canadian Institutes of Health Research
- John C Whitney
Natural Sciences and Engineering Research Council of Canada
- Adrian J Verster
Wellcome (101824/Z/13/Z)
- Waldemar Vollmer
National Cancer Institute (CCSG P30 CA060553)
- Young Ah Goo
National Institutes of Health (AI080609)
- Joseph D Mougous
Howard Hughes Medical Institute
- Joseph D Mougous
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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