Bacterial Flagellin Stimulates Toll-Like Receptor 5-Dependent Defense against Vancomycin-Resistant Enterococcus Infection

Kinnebrew, Melissa A.; Ubeda, Carles; Zenewicz, Lauren A.; Smith, Nichole; Flavell, Richard A.; Pamer, Eric G.
February 2010
Journal of Infectious Diseases;2/15/2010, Vol. 201 Issue 4, p534
Academic Journal
Treatment of vancomycin-resistant Enterococcus (VRE) infections is limited by the paucity of effective antibiotics. Administration of broad-spectrum antibiotics promotes VRE colonization by down-regulating homeostatic innate immune defenses. Intestinal epithelial cells and Paneth cells express antimicrobial factors on direct or indirect stimulation of the Toll-like receptor (TLR)-myeloid differentiation factor 88-mediated pathway by microbederived molecules. Here, we demonstrate that the TLR5 agonist flagellin restores antibiotic-impaired innate immune defenses and restricts colonization with VRE. Flagellin stimulates the expression of RegIIIγ, a secreted C-type lectin that kills gram-positive bacteria, including VRE. Systemic administration of flagellin induces RegIIIγ expression in intestinal epithelial cells and Paneth cells along the entire length of the small intestine. Induction of RegIIIγ requires TLR5 expression in hematopoietic cells and is dependent on interleukin 22 expression. Systemic administration of flagellin to antibiotic-treated mice dramatically reduces VRE colonization. By enhancing mucosal resistance to multidrug-resistant organisms, flagellin administration may provide a clinically useful approach to prevent infections in patients treated with broad-spectrum antibiotics.


Related Articles

  • A Web-Based Multidrug-Resistant Organisms Surveillance and Outbreak Detection System with Rule-Based Classification and Clustering. Tseng, Yi-Ju; Wu, Jung-Hsuan; Ping, Xiao-Ou; Lin, Hui-Chi; Chen, Ying-Yu; Shang, Rung-Ji; Chen, Ming-Yuan; Lai, Feipei; Chen, Yee-Chun // Journal of Medical Internet Research;Sep/Oct2012, Vol. 14 Issue 5, p25 

    Background: The emergence and spread of multidrug-resistant organisms (MDROs) are causing a global crisis. Combating antimicrobial resistance requires prevention of transmission of resistant organisms and improved use of antimicrobials. Objectives: To develop a Web-based information system for...

  • Antimicrobial Resistance to Linezolid. Meka, Venkata G.; Gold, Howard S. // Clinical Infectious Diseases;10/1/2004, Vol. 39 Issue 7, p1010 

    Acquired resistance to linezolid, the first approved oxazolidinone, has been selected in laboratory experiments and has been observed in clinical isolates of gram-positive cocci. This resistance has typically been associated with single-nucleotide changes in varying numbers of copies of the...

  • Antimicrobial resistance in Gram-positive bacteria from Timorese River Buffalo ( Bubalus bubalis) skin microbiota. Oliveira, Manuela; Monteiro, José L.; Rana, Sílvia; Vilela, Cristina L. // Tropical Animal Health & Production;Jun2010, Vol. 42 Issue 5, p833 

    The Timorese River Buffalo ( Bubalus bubalis) plays a major role in the East Timor economy, as it is an important source of animal protein in human nutrition. They are widely spread throughout the country and are in direct contact with the populations. In spite of this proximity, information on...

  • Global network analysis of drug tolerance, mode of action and virulence in methicillin-resistant S. aureus. Overton, Ian M.; Graham, Shirley; Gould, Katherine A.; Hinds, Jason; Botting, Catherine H.; Shirran, Sally; Barton, Geoffrey J.; Coote, Peter J. // BMC Systems Biology;2011, Vol. 5 Issue 1, p68 

    Background: Staphylococcus aureus is a major human pathogen and strains resistant to existing treatments continue to emerge. Development of novel treatments is therefore important. Antimicrobial peptides represent a source of potential novel antibiotics to combat resistant bacteria such as...

  • Multidrug-resistant tuberculosis in Russia: clinical characteristics, analysis of second-line drug resistance and development of standardized therapy. Balabanova, Y.; Ruddy, M.; Hubb, J.; Yates, M.; Malomanova, N.; Fedorin, I.; Drobniewski, F. // European Journal of Clinical Microbiology & Infectious Diseases;Feb2005, Vol. 24 Issue 2, p136 

    The aim of the study presented here was to identify patients with multidrug resistant tuberculosis (MDRTB) in the Samara region of Russia and to analyze the susceptibility of their isolates to second-line drugs in order to develop an empirical, standard, second-line treatment regimen. Treatment...

  • Prevalence of Vancomycin-Resistant Enterococci colonization and its risk factors in chronic hemodialysis patients in Shiraz, Iran. Assadian, Ojan; Askarian, Mehrdad; Stadler, Maria; Shaghaghian, Soheila // BMC Infectious Diseases;2007, Vol. 7 Issue 1, p52 

    Background: Vancomycin-resistant entrococci (VRE) are increasing in prevalence at many institutions, and are often reported in dialysis patients. The aim of this cross-sectional prevalence study was to determine the prevalence and risk factors of VRE colonization in chronic hemodialysis patients...

  • The management of infections due to drug-resistant gram-positive bacteria. Moellering, R. // European Journal of Clinical Microbiology & Infectious Diseases;Dec2005, Vol. 24 Issue 12, p777 

    The article focuses on the management of infections due to drug-resistant gram-positive bacteria. The development of resistance to vancomycin by enterococci is, without doubt, one of the more remarkable bacterial achievements because of the complexity of the genetic elements necessary for such...

  • Prospective Surveillance of Vancomycin-Resistant Enterococci in a Neonatal Intensive Care Unit. Toledano, H.; Schlesinger, Y.; Raveh, D.; Rudensky, B.; Attias, D.; Eidelman, A. I.; Yinnon, A. M. // European Journal of Clinical Microbiology & Infectious Diseases;Apr2000, Vol. 19 Issue 4, p282 

    A point-prevalence study of vancomycin-resistant enterococci colonization of the gastrointestinal tract in an Israeli hospital revealed that 14.7% of the 320 inpatients were colonized. Vancomycin-resistant enterococci colonization was detected in most departments except the neonatal intensive...

  • Preventing the Influx of Vancomycin-Resistant Enterococci into Health Care Institutions, by Use of a Simple Validated Prediction Rule. Tacconelli, Evelina; Karchmer, Adolf W.; Yokoe, Deborah; D'Agata, Erika M. C. // Clinical Infectious Diseases;10/1/2004, Vol. 39 Issue 7, p964 

    Background. The goal of this study was to develop a validated prediction rule for identification of patients harboring vancomycin-resistant enterococci (VRE) at hospital admission. Methods. A model for the prediction of patients harboring VRE at admission was created and validated by assigning...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics