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• Antibiotic-resistant bacteria: why are they so successful?

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         description:Why antibiotic-resistant bacteria are so successful at causing infections in patients being treated with antibiotics is a something of a mystery. One previously unrecognized factor is reported in this issue: treatment with the broad-spectrum antibiotic vancomycin increases infection with resistant bacteria by compromising intestinal innate immunity. In mice receiving the antibiotic, intestinal expression of the antimicrobial protein, RegIIIγ was suppressed. RegIIIγ is notably effective against vancomycin-resistant Enterococcus (VRE), a common infection in hospitalized patients. Therapies that increase levels of this protein, such as orally administered lipopolysaccharide, may therefore be of use in patients receiving broad-spectrum antibiotics. Infection with antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a dangerous and costly complication of broad-spectrum antibiotic therapy1,2. 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.
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            name:Present addresses: Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (K.B.); Department of Infectious Diseases, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA (C.N.M.); Department of Medicine, University of California San Diego, La Jolla, California 92093, USA (B.S.).
            address:
               name:Present addresses: Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (K.B.); Department of Infectious Diseases, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA (C.N.M.); Department of Medicine, University of California San Diego, La Jolla, California 92093, USA (B.S.).,
               type:PostalAddress
            type:Organization
      name:Carles Ubeda
      affiliation:
            name:Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute
            address:
               name:Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute,
               type:PostalAddress
            type:Organization
      name:Ting Jia
      affiliation:
            name:Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute
            address:
               name:Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute,
               type:PostalAddress
            type:Organization
      name:Martin Fleisher
      affiliation:
            name:Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
            address:
               name:Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA,
               type:PostalAddress
            type:Organization
      name:Bernd Schnabl
      affiliation:
            name:Columbia University, New York, New York 10032, USA
            address:
               name:Department of Medicine, Columbia University, New York, New York 10032, USA,
               type:PostalAddress
            type:Organization
            name:Present addresses: Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (K.B.); Department of Infectious Diseases, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA (C.N.M.); Department of Medicine, University of California San Diego, La Jolla, California 92093, USA (B.S.).
            address:
               name:Present addresses: Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (K.B.); Department of Infectious Diseases, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA (C.N.M.); Department of Medicine, University of California San Diego, La Jolla, California 92093, USA (B.S.).,
               type:PostalAddress
            type:Organization
      name:Ronald P. DeMatteo
      affiliation:
            name:Hepatobiliary Service,
            address:
               name:Hepatobiliary Service,,
               type:PostalAddress
            type:Organization
      name:Eric G. Pamer
      affiliation:
            name:Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute
            address:
               name:Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute,
               type:PostalAddress
            type:Organization
            name:Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
            address:
               name:Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA,
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute,
      name:Present addresses: Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (K.B.); Department of Infectious Diseases, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA (C.N.M.); Department of Medicine, University of California San Diego, La Jolla, California 92093, USA (B.S.).,
      name:Hepatobiliary Service,,
      name:Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute,
      name:Present addresses: Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (K.B.); Department of Infectious Diseases, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA (C.N.M.); Department of Medicine, University of California San Diego, La Jolla, California 92093, USA (B.S.).,
      name:Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute,
      name:Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute,
      name:Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA,
      name:Department of Medicine, Columbia University, New York, New York 10032, USA,
      name:Present addresses: Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (K.B.); Department of Infectious Diseases, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA (C.N.M.); Department of Medicine, University of California San Diego, La Jolla, California 92093, USA (B.S.).,
      name:Hepatobiliary Service,,
      name:Department of Medicine, Infectious Diseases Service, Immunology Program, Sloan-Kettering Institute,
      name:Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA,
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