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Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans
Open accessAbstract
Bloodstream infection by highly antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a growing clinical problem that increasingly defies medical intervention. Identifying patients at high risk for bacterial sepsis remains an important clinical challenge. Recent studies have shown that antibiotics can alter microbial diversity in the intestine. Here, we characterized these effects using 16s rDNA pyrosequencing and demonstrated that antibiotic treatment of mice enabled exogenously administered VRE to efficiently and nearly completely displace the normal microbiota of the small and large intestine. In the clinical setting, we found that intestinal domination by VRE preceded bloodstream infection in patients undergoing allogeneic hematopoietic stem cell transplantation. Our results demonstrate that antibiotics perturb the normal commensal microbiota and set the stage for intestinal domination by bacteria associated with hospital-acquired infections. Thus, high-throughput DNA sequencing of the intestinal microbiota could identify patients at high risk of developing bacterial sepsis.
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“Each of these outcomes, as well as overall survival, has been associated in single-center studies with features of the intestinal microbiota in the period after hematopoietic-cell transplantation.2–4,8–15”
From Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation (2020) · cites this paper as [13]
In the citing paper
“Gram− commensals can be depleted by vancomycin, which is a Gram+-targeting drug [83].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [83]
In the citing paper
“VRE colonizes the intestine following antibiotic treatment, prior to spreading to the bloodstream, and thus, represents a major threat for hospitalized patients [83].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [83]
In the citing paper
“The taxonomic composition of the gut microbiota changes throughout the gastrointestinal tract, according to nutrient availability, mucus structure, pH and oxygen availability [1–6].”
From Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization (2023) · cites this paper as [3]
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Gut Microbiota and Antibiotics: Dysbiosis and Antimicrobial Resistance
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The Post-HCT Intestinal Microbiome: Who are the Key Disruptors and How Long does the Damage Last?
Markey, K. A. (2022) · Transplantation and Cellular Therapy · doi:10.1016/j.jtct.2022.02.005 · Cited by 1
Miscellaneous antibacterial drugs
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Origin of intraradicular infection with Enterococcus faecalis in endodontically treated teeth
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Guervil, D. J., Klinker, K. P., Reardon, N. T., Alnuaimat, H., Borgert, S. J., & Ramphal, R. (2013) · Infection Control and Hospital Epidemiology · doi:10.1086/674403 · Cited by 1
Rattanaprasert, M. (2015) · Lincoln (University of Nebraska) · Cited by 1
Enterococcus faecalis modulation of NF-kB signaling in macrophages
Bhaduri-Tagore, S. (2016) · doi:10.32657/10356/69063 · Cited by 1
Interplay between gut microbiota and antibiotics
Gonzalez, T. D. J. B. (2016) · doi:10.18174/394954 · Cited by 1
Flor‐Duro, A. (2021) · RiuNet (Universitat Politècnica de València) · doi:10.4995/thesis/10251/166494 · Cited by 1
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Antibiotic-Associated Diarrhea
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Phage-specific immune responses impair efficacy of phage therapy targeting VRE in a murine modelPreprint
Berkson, J. D., Allen, G. B., Schubert, A. M., Dunbar, K. E., Coryell, M. P., Sava, R. L., Gao, Y. S., Wate, C. E., Hastie, J. L., Zimmermann, S. K., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.19.523600 · Cited by 1
Metadata
- Authors
- Ubeda, C., Taur, Y., Jenq, R. R., Equinda, M. J., Son, T., Samstein, M., Viale, A., Socci, N. D., van den Brink, M. R. M., Kamboj, M., & Pamer, E. G.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2010-12-01
- Volume
- 120
- Issue
- 12
- Pages
- 4332-4341
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2993598
- OpenAlex
- W1979573684
- Cited by
- 943
- References
- 51
- Citations by year
- 2026: 52 · 2025: 48 · 2024: 55 · 2023: 58 · 2022: 94 · 2021: 72 · 2020: 76 · 2019: 90 · 2018: 64 · 2017: 66 · 2016: 56 · 2015: 49 · 2014: 44 · 2013: 51 · 2012: 46
- FWCI
- 15.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- National Institutes of Health (4r37ai039031-21, CA023766)
- National Cancer Institute (P01CA023766, R01CA107096, P30CA008748)
- National Institute of General Medical Sciences (T32GM007739)
- National Institute of Allergy and Infectious Diseases (R37-AI039031, R01AI080455, K23AI083880, R01AI042135)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Keywords
- vancomycin-resistant enterococci, antibiotic-induced dysbiosis, gut microbiota, bacterial sepsis, bloodstream infection, allogeneic hematopoietic stem cell transplantation, nosocomial infections, sepsis risk prediction
- MeSH terms
- Animals, Anti-Bacterial Agents, Base Sequence, Cross Infection, DNA, Bacterial, DNA, Ribosomal, Humans, Intestines, Mice, Inbred C57BL, Bacteremia, Gram-Positive Bacterial Infections, Enterococcus, Hematopoietic Stem Cell Transplantation, Vancomycin Resistance, Mice, Metagenome
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