Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits

By K. Brandl, G. Plitas, C. Mihu, C. Ubeda, Ting Jia, M. Fleisher, B. Schnabl, R. DeMatteo, Eric G. Pamer. Nature, 2008

633 citations recorded by the source corpus.

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.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/c5163fc1b15593d66d6090e52283f0008ca5770f

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Citations in the corpus

The rise of the Enterococcus: beyond vancomycin resistance (2012, methodology): “Pioneering work using mouse models of intestinal colonizatio”
Impact of antibiotics on the human microbiome and consequences for host health (2022, background): “Germ‐free mice colonized with conventional or human mi- crobiota or specific probiotic species or LPS demonstrated increased production of antimicrobial peptides like REGIII‐γ, boosting the in- nate immune response (Brandl et al., 2008; Cash et al., 2006; Natividad et al., 2013).”
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The Microbiome in Infectious Disease and Inflammation (2012, positive): “Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection.”
Role of the Microbiota in Immunity and inflammation (2014, background): “…antimicrobial peptide RegIIIg not only contributes to maintenance of segregation between the microbiota and host epithelial cells, but also promotes protection against defined pathogens, such as vancomycin-resistant Enterococcus faecalis (Brandl et al., 2008; Vaishnava et al., 2008, 2011).”
Nod2 is required for the regulation of commensal microbiota in the intestine (2009, background): “MyD88 also is known to control intestinal infection by pathogenic bacteria such as Listeria monocytogenes or vancomycin-resistant Enterococcus through an increased expression of antimicrobials (32, 33).”
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RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota (2011, background): “Perturbation of homeostasis leads either to inflammatory disease characterized by immune attack on microbial symbionts and tissue destruction, the scenario that unfolds during inflammatory bowel disease, or (in contrast) to low reactivity of the intestinal immune system and greater susceptibility to”