SpeB of Streptococcus pyogenes differentially modulates antibacterial and receptor

Background: CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP–10/ CXCL10 and I–TAC/CXCL11, are antibacterial for Streptococcus pyogenes. Methodology/Principal Findings: SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/ CXCL11, PF4/CXCL4, GROa/CXCL1, GROb/CXCL2, GROc/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3a/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3a/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. Conclusions/Significance: SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium. Citation: Egesten A, Olin AI, Linge HM, Yadav M, Mörgelin M, et al. (2009) SpeB of Streptococcus pyogenes Differentially Modulates Antibacterial and Receptor Activating Properties of Human Chemokines. PLoS ONE 4(3): e4769. doi:10.1371/journal.pone.0004769 Editor: Adam J. Ratner, Columbia University, United States of America Received November 24, 2008; Accepted January 31, 2009; Published March 10, 2009 Copyright: 2009 Egesten et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the Swedish Research Council (projects 2005-4791 and 2007-2880), the Swedish Heart and Lung Foundation, the Foundations of Crafoord, Jeansson, Zoéga, Kock, Bergh, Bergvall, Hedberg, Österlund, Groschinsky, the Swedish Society of Medicine, the Royal Physiografic Society, and the Medical Faculty at Lund University. M.C. is the recipient of an Assistant Professorship from the Swedish Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] ¤a Current address: Section for Cardiopulmonary Research, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America ¤b Current address: Division of Microbiology, Immunology and Glycobiology (MIG), Department of Laboratory Medicine, Lund University, Lund, Sweden