Are There Bad ICU Rooms? Temporal Relationship between Patient and ICU Room Microbiome, and Influence on Vancomycin-Resistant Enterococcus Colonization.

The gut microbiome of an individual can shape the local environmental surface microbiome. We sought to determine how the intensive care unit (ICU) patient gut microbiome shapes the ICU room surface microbiome, focusing on vancomycin-resistant Enterococcus (VRE), a common ICU pathogen. This was an ICU-based prospective cohort study. Rectal swabs were performed in adult ICU patients immediately at the time of ICU admission and environmental surface swabs were performed at five predetermined time points. All swabs underwent 16S rRNA gene sequencing and culture for VRE. 304 ICU patients and 24 ICU rooms were sampled (5 longitudinal samples per ICU room). Spatially adjacent ICU rooms were no more microbially similar than nonadjacent rooms. Microbial signatures within rooms diverged rapidly over time: in 14 days, ICU rooms were as similar to other ICU rooms as they were to their prior selves. This divergence over time was more pronounced in rooms with higher patient turnover. Examining VRE status by culture, patient VRE gut colonization had modest agreement with room surface VRE (kappa statistic 0.36). There were no ICU rooms that consistently cultured positive for VRE, including those that housed VRE positive patients. Individual ICU patients had a limited impact on ICU room surface microbiome, and rooms diverged similarly over time regardless of patients. Patient VRE gut colonization may have a modest influence on room surface VRE but there were no "bad rooms" that consistently cultured positive for VRE. These results may be useful in planning infection control measures. IMPORTANCE This study found that intensive care unit (ICU) room microbial signatures diverged from their baseline quickly: within 2 weeks, individual ICU rooms had lost distinguishing characteristics and were as similar to other ICU rooms as they were to their former selves. Patient turnover within rooms accelerated this drift. Patient gut colonization with vancomycin-resistant Enterococcus (VRE) was associated with ICU room surface contamination with VRE; again, within 2 weeks, this association was substantially diminished. These results provide dynamic information regarding how patients control the microbiota on local hospital room surfaces and may facilitate decision making for infection prevention and control measures targeting VRE or other organisms.

Runx1 Role in Epithelial and Cancer Cell Proliferation Implicates Lipid Metabolism and Scd1 and Soat1 Activity.

The role of lipid metabolism in epithelial stem cell (SC) function and carcinogenesis is poorly understood. The transcription factor Runx1 is known to regulate proliferation in mouse epithelial hair follicle (HF) SCs in vivo and in several mouse and human epithelial cancers. We found a novel subset of in vivo Runx1 HFSC target genes related to lipid metabolism and demonstrated changes in distinct classes of lipids driven by Runx1. Inhibition of lipid-enzymes Scd1 and Soat1 activity synergistically reduces proliferation of mouse skin epithelial cells and of human skin and oral squamous cell carcinoma cultured lines. Varying Runx1 levels induces changes in skin monounsaturated fatty acids (e.g., oleate, a product of Scd1) as shown by our lipidome analysis. Furthermore, varying Runx1 levels, the inhibition of Scd1, or the addition of Scd1-product oleate, individually affects the plasma membrane organization (or fluidity) in mouse keratinocytes. These factors also affect the strength of signal transduction through the membranes for Wnt, a pathway that promotes epithelial (cancer) cell proliferation and HFSC activation. Our working model is that HFSC factor Runx1 modulates the fatty acid production, which affects membrane organization, facilitating signal transduction for rapid proliferation of normal and cancer epithelial cells. Stem Cells 2018;36:1603-1616.