Vancomycin-resistance gene cluster, vanC, in the gut microbiome of acute leukemia patients undergoing intensive chemotherapy

PLoS One. 2019 Oct 10;14(10):e0223890. doi: 10.1371/journal.pone.0223890. eCollection 2019.

Abstract

Two recent reports suggested that the less common, less virulent enterococcal species, Enterococcus gallinarum and E. casseliflavus, with low-level vancomycin resistance due to chromosomally encoded vanC1 and vanC2/3, may influence host immunity. We reported that peri-transplant gut colonization with E. gallinarum and E. casseliflavus is associated with lower mortality after allogeneic hematopoietic cell transplantation (HCT). Because most acute leukemia patients undergoing HCT have received intensive chemotherapy (usually requiring prolonged hospitalization) for their underlying disease before HCT, we hypothesized that some may have acquired vanC-positive enterococci during chemotherapy. Therefore, we evaluated the presence of the vanC gene cluster using vanC1 and vanC2/3 qPCR in thrice-weekly collected stool samples from 20 acute leukemia patients undergoing intensive chemotherapy. We found that an unexpectedly large proportion of patients have detectable vanC1 and vanC2/3 (15% and 35%, respectively) in at least one stool sample. Comparing qPCR results with 16S rRNA gene sequencing results suggested that E. gallinarum may reach high abundances, potentially persisting into HCT and influencing transplant outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections / prevention & control
  • Bacterial Proteins / genetics*
  • DNA Barcoding, Taxonomic
  • Drug Resistance, Bacterial*
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / microbiology*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • RNA, Ribosomal, 16S / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • RNA, Ribosomal, 16S
  • VanC protein, Bacteria

Grants and funding

This work was supported by grants from the University of Minnesota (Medical School Innovation award and Foundation grant for new faculty) to AR. In addition, funding from Achieving Cures Together and Hubbard Broadcasting Foundation supported this research. TK received partial support from the Masonic Cancer Center at the University of Minnesota. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.