Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits Journal Article
| Authors: | Brandl, K.; Plitas, G.; Mihu, C. N.; Ubeda, C.; Jia, T.; Fleisher, M.; Schnabl, B.; DeMatteo, R. P.; Pamer, E. G. |
| Article Title: | Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits |
| Abstract: | Infection with antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a dangerous and costly complication of broad-spectrum antibiotic therapy. How antibiotic-mediated elimination of commensal bacteria promotes infection by antibiotic-resistant bacteria is a fertile area for speculation with few defined mechanisms. Here we demonstrate that antibiotic treatment of mice notably downregulates intestinal expression of RegIIIγ (also known as Reg3g), a secreted C-type lectin that kills Gram-positive bacteria, including VRE. Downregulation of RegIIIγ markedly decreases in vivo killing of VRE in the intestine of antibiotic-treated mice. Stimulation of intestinal Toll-like receptor 4 by oral administration of lipopolysaccharide re-induces RegIIIγ, thereby boosting innate immune resistance of antibiotic-treated mice against VRE. Compromised mucosal innate immune defence, as induced by broad-spectrum antibiotic therapy, can be corrected by selectively stimulating mucosal epithelial Toll-like receptors, providing a potential therapeutic approach to reduce colonization and infection by antibiotic-resistant microbes. ©2008 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | signal transduction; protein expression; antibiotic agent; antibiotic therapy; unclassified drug; nonhuman; proteins; mouse; animals; mice; mus; immune system; gene expression; animal experiment; animal model; down-regulation; gene expression regulation; toll like receptor 4; antibiotic resistance; protein induction; lipopolysaccharide; innate immunity; down regulation; rodent; enterococcus; vancomycin resistance; bacterial colonization; vancomycin; metronidazole; intestines; myeloid differentiation factor 88; bacterium; enterococcal infection; experimental study; toll-like receptor 4; clindamycin; neomycin; gastrointestinal infection; lipopolysaccharides; dectin 2; enrofloxacin; regiiigamma protein; bacterial disease; enterococcaceae; vancomycin resistant enterococci; immunity, natural; posibacteria |
| Journal Title: | Nature |
| Volume: | 455 |
| Issue: | 7214 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2008-10-09 |
| Start Page: | 804 |
| End Page: | 807 |
| Language: | English |
| DOI: | 10.1038/nature07250 |
| PUBMED: | 18724361 |
| PROVIDER: | scopus |
| PMCID: | PMC2663337 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 78" - "Export Date: 17 November 2011" - "CODEN: NATUA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work