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

Caballero S, Carter R, Ke X, Sušac B, Leiner IM, Kim GJ, Miller L, Ling L, Manova K, Pamer EG - PLoS Pathog. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Immunology Program and Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, New York, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Fecal bacteriotherapy eliminates established K. pneumoniae and VRE intestinal domination.(A) Experimental design. Mice were treated with ampicillin for 8 days. On day 5 of ampicillin treatment, mice were simultaneously infected with 5x104 CFU of VRE and K. pneumoniae (Kpn). Three days post infection, ampicillin treatment was stopped. Mice were administered PBS or a fecal microbiota transplant (FMT) from an untreated mouse on three consecutive days starting on the third day after ampicillin cessation. (B, C) VRE and K. pneumoniae burden was quantified in fecal pellets at the indicated time points after the last PBS (B) or FMT (C) dose. (D, E) PBS- and FMT-treated mice were sacrificed on day 10 following the last treatment dose and numbers of K. pneumoniae (D) and VRE (E) CFU were quantified in the duodenum, ileum and cecum. L.O.D., limit of detection. n ≥ 5 per group. (B-E) **P<0.005 by the Mann-Whitney test.
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ppat.1005132.g004: Fecal bacteriotherapy eliminates established K. pneumoniae and VRE intestinal domination.(A) Experimental design. Mice were treated with ampicillin for 8 days. On day 5 of ampicillin treatment, mice were simultaneously infected with 5x104 CFU of VRE and K. pneumoniae (Kpn). Three days post infection, ampicillin treatment was stopped. Mice were administered PBS or a fecal microbiota transplant (FMT) from an untreated mouse on three consecutive days starting on the third day after ampicillin cessation. (B, C) VRE and K. pneumoniae burden was quantified in fecal pellets at the indicated time points after the last PBS (B) or FMT (C) dose. (D, E) PBS- and FMT-treated mice were sacrificed on day 10 following the last treatment dose and numbers of K. pneumoniae (D) and VRE (E) CFU were quantified in the duodenum, ileum and cecum. L.O.D., limit of detection. n ≥ 5 per group. (B-E) **P<0.005 by the Mann-Whitney test.

Mentions: Transplantation of feces from donor mice that have not been treated with antibiotics can eliminate VRE from the intestine of densely colonized mice and, in humans, fecal transplantation from healthy donors cures patients with recurrent Clostridium difficile infection [11, 24]. To determine whether the kinetics of VRE and K. pneumoniae clearance from the murine intestine following fecal transplantation are similar or distinct, we colonized ampicillin-treated mice with VRE and K. pneumoniae concurrently, terminated ampicillin treatment and treated mice with fecal microbiota transplants (FMT) or PBS on three consecutive days (Fig 4A). VRE and K. pneumoniae colonization levels were similar in the feces before FMT administration and remained elevated in mice that received PBS instead of FMT (Fig 4B). However, following FMT treatment, K. pneumoniae density in fecal pellets decreased within one day and became undetectable within 7 days in all mice (Fig 4C). VRE, on the other hand, was cleared in 60% of the mice but reduced by 3 logs in the remaining 40%. Increased colonization resistance against K. pneumoniae as opposed to VRE was also observed in mice that had not been treated with antibiotics (S1A Fig). K. pneumoniae was also cleared more effectively than VRE from the duodenum, ileum and cecum of FMT-treated animals while the density of these bacterial species remained high in PBS-treated mice (Fig 4D and 4E). These findings suggest that the mechanisms of microbiota-mediated colonization resistance against VRE and K. pneumoniae are distinct or that K. pneumoniae is more susceptible to colonization resistance.


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

Caballero S, Carter R, Ke X, Sušac B, Leiner IM, Kim GJ, Miller L, Ling L, Manova K, Pamer EG - PLoS Pathog. (2015)

Fecal bacteriotherapy eliminates established K. pneumoniae and VRE intestinal domination.(A) Experimental design. Mice were treated with ampicillin for 8 days. On day 5 of ampicillin treatment, mice were simultaneously infected with 5x104 CFU of VRE and K. pneumoniae (Kpn). Three days post infection, ampicillin treatment was stopped. Mice were administered PBS or a fecal microbiota transplant (FMT) from an untreated mouse on three consecutive days starting on the third day after ampicillin cessation. (B, C) VRE and K. pneumoniae burden was quantified in fecal pellets at the indicated time points after the last PBS (B) or FMT (C) dose. (D, E) PBS- and FMT-treated mice were sacrificed on day 10 following the last treatment dose and numbers of K. pneumoniae (D) and VRE (E) CFU were quantified in the duodenum, ileum and cecum. L.O.D., limit of detection. n ≥ 5 per group. (B-E) **P<0.005 by the Mann-Whitney test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559429&req=5

ppat.1005132.g004: Fecal bacteriotherapy eliminates established K. pneumoniae and VRE intestinal domination.(A) Experimental design. Mice were treated with ampicillin for 8 days. On day 5 of ampicillin treatment, mice were simultaneously infected with 5x104 CFU of VRE and K. pneumoniae (Kpn). Three days post infection, ampicillin treatment was stopped. Mice were administered PBS or a fecal microbiota transplant (FMT) from an untreated mouse on three consecutive days starting on the third day after ampicillin cessation. (B, C) VRE and K. pneumoniae burden was quantified in fecal pellets at the indicated time points after the last PBS (B) or FMT (C) dose. (D, E) PBS- and FMT-treated mice were sacrificed on day 10 following the last treatment dose and numbers of K. pneumoniae (D) and VRE (E) CFU were quantified in the duodenum, ileum and cecum. L.O.D., limit of detection. n ≥ 5 per group. (B-E) **P<0.005 by the Mann-Whitney test.
Mentions: Transplantation of feces from donor mice that have not been treated with antibiotics can eliminate VRE from the intestine of densely colonized mice and, in humans, fecal transplantation from healthy donors cures patients with recurrent Clostridium difficile infection [11, 24]. To determine whether the kinetics of VRE and K. pneumoniae clearance from the murine intestine following fecal transplantation are similar or distinct, we colonized ampicillin-treated mice with VRE and K. pneumoniae concurrently, terminated ampicillin treatment and treated mice with fecal microbiota transplants (FMT) or PBS on three consecutive days (Fig 4A). VRE and K. pneumoniae colonization levels were similar in the feces before FMT administration and remained elevated in mice that received PBS instead of FMT (Fig 4B). However, following FMT treatment, K. pneumoniae density in fecal pellets decreased within one day and became undetectable within 7 days in all mice (Fig 4C). VRE, on the other hand, was cleared in 60% of the mice but reduced by 3 logs in the remaining 40%. Increased colonization resistance against K. pneumoniae as opposed to VRE was also observed in mice that had not been treated with antibiotics (S1A Fig). K. pneumoniae was also cleared more effectively than VRE from the duodenum, ileum and cecum of FMT-treated animals while the density of these bacterial species remained high in PBS-treated mice (Fig 4D and 4E). These findings suggest that the mechanisms of microbiota-mediated colonization resistance against VRE and K. pneumoniae are distinct or that K. pneumoniae is more susceptible to colonization resistance.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Immunology Program and Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, New York, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus