@article{042eb434a15c43858407f9720d17c483,
title = "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 contactand 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.",
author = "Whitney, {John C.} and Peterson, {S. Brook} and Jungyun Kim and Manuel Pazos and Verster, {Adrian J.} and Radey, {Matthew C.} and Kulasekara, {Hemantha D.} and Ching, {Mary Q.} and Bullen, {Nathan P.} and Diane Bryant and Goo, {Young Ah} and Surette, {Michael G.} and Elhanan Borenstein and Waldemar Vollmer and Mougous, {Joseph D.}",
note = "Funding Information: We thank Eefjan Breukink for providing lipid II, Joe Gray for mass spectrometry analyses, the Fang and Rajagopal laboratories for sharing reagents, Lynn Hancock and Gary Dunny for providing strains and plasmids, Corie Ralston for help with X-ray data collection, Ben Ross and Simon Dove for critical reading of the manuscript, and members of the Mougous laboratory for helpful discussions. This work was funded by the NIH (AI080609 to JDM and AT007802 to EB), the Defense Threat Reduction Agency (HDTRA1-13-1-0014 to JDM), and the Medical Research Council (MR/N0026791/1). Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569. JCW was supported by a postdoctoral research fellowship from the Canadian Institutes of Health Research, AJV was supported by a postdoctoral fellowship from the Natural Science and Engineering Research Council of Canada, and JDM holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund and is an HHMI Investigator. Publisher Copyright: {\textcopyright} Whitney et al.",
year = "2017",
month = jul,
day = "11",
doi = "10.7554/eLife.26938",
language = "English",
volume = "6",
journal = "eLife",
issn = "2050-084X",
}