Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium

Abstract

SUMMARY Antibiotic-mediated microbiota destruction and the consequent loss of colonization resistance can result in intestinal domination with vancomycin-resistant Enterococcus (VRE), leading to bloodstream infection in hospitalized patients. Clearance of VRE remains a challenging goal that, if achieved, would reduce systemic VRE infections and patient-to-patient transmission. Although obligate anaerobic commensal bacteria have been associated with colonization resistance to VRE, the specific bacterial species involved remain undefined. Herein we demonstrate that a precisely defined consortium of commensal bacteria containing the Clostridium cluster XIVa species Blautia producta and Clostridium bolteae restores colonization resistance against VRE and clears VRE from the intestines of mice. While C. bolteae did not directly mediate VRE clearance it enabled intestinal colonization with B. producta, which directly inhibited VRE growth. These findings suggest that therapeutic or prophylactic administration of defined bacterial consortia to individuals with compromised microbiota composition may reduce inter-patient transmission and intra-patient dissemination of highly antibiotic-resistant pathogens.

Comprehensive analysis of mobile genetic elements in the gut microbiome reveals phylum-level niche-adaptive gene pools

“…Our results suggest that HGT occurs mostly within a phylum, and inter-phyla HGT is 366 rare. These results underscore the risk posed by transfer of antibiotic resistance genes like the 367 vancomycin-resistance conferring gene VanB between commensal Firmicutes and pathogenic Firmicutes, 368 such as Enterococcus faecalis 69 . Overall, our study advances the understanding of the host range of MGEs 369 which is of critical importance to understand gene flow networks in the gut.…”

Allied Commensal Forces against Vancomycin-Resistant Enterococci

“…What generally enables VRE clearance is unlikely specific species and more likely specific redundant functions shared by many different combinations of species in specific niches. As the authors also acknowledge, it is unclear whether the specific consortium defined in this study from Caballero et al (2017) will be efficacious for VRE clearance in humans. Without understanding the mechanisms involved, which were also acknowledged as likely being complex and redundant, treatment with a specific taxonomic definition may not be generally applicable.…”

“… In this issue of Cell Host & Microbe , Caballero et al (2017) define a precise, limited consortium of commensal bacteria that restores resistance to colonization by clinically vexing vancomycin-resistant Enterococcus species. …”

“…in the gut microbiota were “protected” against VRE colonization and bloodstream infections suggested translatability of this finding (Ubeda et al, 2013). Building upon this set of observations, now Caballero et al (2017) attempt to identify a “minimal consortium” capable of clearing VRE. In order to hone in on such a “minimal consortium,” two compositionally different communities, both of which are functionally capable of restoring VRE resistance, were investigated.…”

The gut microbiota of critically ill patients: first steps in an unexplored world

“…Interestingly, certain commensals may exert species-specific colonization resistance: Clostridium bolteae and Blautia producta act synergistically to prevent the acquisition of vancomycin-resistant enterococci (VRE) [12]; colonization with Clostridium scindens appears to protect from Clostridium difficile infection [13]; while members of the Desulfovibrio, Oscillospira, Parabacteroides, or Coprococcus genera have been associated with the absence of carriage of extendedspectrum beta-lactamase-producing Escherichia coli [14]. Of note, both 16S profiling and shotgun metagenomics only address the dominant fraction of the microbiota and, therefore, do not detect pathogens unless their relative fecal abundance increases sharply, most often following antimicrobial exposure.…”