Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae

Abstract

Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs.

Fecal Microbiota Transplantation in Patients With Blood Disorders Inhibits Gut Colonization With Antibiotic-Resistant Bacteria: Results of a Prospective, Single-Center Study

“…following FMT was associated with elimination of VRE [6]. Recently, Caballero et al showed that VRE occupies niches in the GI tract that overlap spatially with those occupied by K. pneumoniae [7]. Our finding, although it relates to a small number of observations, suggests that a high abundance of Barnesiella spp., Bacteroides, and/or Butyricimonas and/or a large number of OTUs in the transplanted fecal material contribute to the eradication of K. pneumoniae.…”

“…Colonized patients pose an epidemiological threat to other hospitalized individuals and to members of their households [6,7] but are also in danger of developing systemic infections with gut-colonizing microorganisms [8,9]. This is especially the case for patients with blood disorders due to suppression of their innate and/or acquired immunity.…”

TLR-7 activation enhances IL-22–mediated colonization resistance against vancomycin-resistant enterococcus

“…Ampicillin administration depletes indigenous intestinal bacterial communities but does not inhibit VRE growth (fig. S1A) (32). As previously reported (32), ampicillin-treated mice became densely colonized with VRE, whereas colonization resistance in ampicillin-naïve control mice prevented intestinal VRE colonization (Fig.…”

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

“…It remains unclear whether bacterial species that confer colonization resistance to VRE similarly protect against Enterobacteriaceae such as antibiotic-resistant Klebsiella pneumoniae . However, at least in mouse models, reestablishment of a normal microbiota in VRE- or K. pneumoniae –dominated mice by transplantation of feces from antibiotic-naïve mice leads to the elimination of both bacterial species (18). With respect to VRE domination, deep 16 S rRNA gene sequence analysis demonstrated a strong correlation between the presence of bacteria belonging to the Barnesiella genus and colonization resistance to VRE (8).…”