西亞試劑：Gram-positive three-component antimicrobial peptide-sensing

Gram-positive three-component antimicrobial peptide-sensing system

Min Li*, Yuping Lai*,,, Amer E. Villaruz*, David J. Cha*, Daniel E. Sturdevant, and Michael Otto*,¶

*Laboratory of Human Bacterial Pathogenesis and Research and Technology Branch, Research Technologies Section, Genomics Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; and School of Life Science, East China Normal University, Shanghai 200062, China

Edited by Emil C. Gotschlich, The Rockefeller University, New York, NY, and approved April 19, 2007 (received for review March 8, 2007)

To survive during colonization or infection of the human body, microorganisms must circumvent mechanisms of innate host defense. Antimicrobial peptides represent a key component of innate host defense, especially in phagocytes and on epithelial surfaces. However, it is not known how the clinically important group of Gram-positive bacteria sense antimicrobial peptides to coordinate a directed defensive response. By determining the genome-wide gene regulatory response to human -defensin 3 in the nosocomial pathogen Staphylococcus epidermidis, we discovered an antimicrobial peptide sensor system that controls major specific resistance mechanisms of Gram-positive bacteria and is unrelated to the Gram-negative PhoP/PhoQ system. It contains a classical two-component signal transducer and an unusual third protein, all of which are indispensable for signal transduction and antimicrobial peptide resistance. Furthermore, our data indicate that a very short, extracellular loop with a high density of negative charges in the sensor protein is responsible for antimicrobial peptide binding and the observed specificity for cationic antimicrobial peptides. Our study shows that Gram-positive bacteria have developed an efficient and unique way of controlling resistance mechanisms to antimicrobial peptides, which may provide a promising target for antimicrobial drug development.

innate host defense | Staphylococcus epidermidis

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