This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hamilton, A. Articles by Jones, A. L. Search for Related Content PubMed PubMed Citation Articles by Hamilton, A. Articles by Jones, A. L.

Penicillin-Binding Protein 1a Promotes Resistance of Group B Streptococcus to Antimicrobial Peptides

Andrea Hamilton,¹ David L. Popham,² David J. Carl,¹ Xavier Lauth,^3, Victor Nizet,³ and Amanda L. Jones^1*

Department of Pediatrics, University of Washington, Seattle, Washington,¹ Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia,² Department of Pediatrics, University of California, San Diego, La Jolla, California³

Received 6 June 2006/ Returned for modification 21 July 2006/ Accepted 4 August 2006

Evasion of host immune defenses is critical for the progression of invasive infections caused by the leading neonatal pathogen, group B streptococcus (GBS). Upon characterizing the factors required for virulence in a neonatal rat sepsis model, we found that a surface-associated penicillin-binding protein (PBP1a), encoded by ponA, played an essential role in resistance of GBS to phagocytic clearance. In order to elucidate how PBP1a promotes resistance to innate immunity, we compared the susceptibility of wild-type GBS and an isogenic ponA mutant to the bactericidal components of human neutrophils. The isogenic strains were found to be equally capable of blocking complement activation on the bacterial surface and equally associated with phagocytes and susceptible to oxidative killing. In contrast, the ponA mutant was significantly more susceptible to killing by cationic antimicrobial peptides (AMPs) of the cathelicidin and defensin families, which are now recognized as integral components of innate host defense against invasive bacterial infection. These observations may help explain the sensitivity to phagocytic killing and attenuated virulence of the ponA mutant. This novel function for PBP1a in promoting resistance of GBS to AMP did not involve an alteration in bacterial surface charge or peptidoglycan cross-linking. While the peptidoglycan polymerization and cross-linking activity of PBPs are essential for bacterial survival, our study is the first to identify a role for a PBP in resistance to host AMPs.

Editor: J. N. Weiser

Present address: Kent SeaTech and Aquabounty Pacific, San Diego, CA.

This article has been cited by other articles:

• Kramer, N. E., Hasper, H. E., van den Bogaard, P. T. C., Morath, S., de Kruijff, B., Hartung, T., Smid, E. J., Breukink, E., Kok, J., Kuipers, O. P. (2008). Increased D-alanylation of lipoteichoic acid and a thickened septum are main determinants in the nisin resistance mechanism of Lactococcus lactis. Microbiology 154: 1755-1762 [Abstract] [Full Text]  
• Maisey, H. C., Quach, D., Hensler, M. E., Liu, G. Y., Gallo, R. L., Nizet, V., Doran, K. S. (2008). A group B streptococcal pilus protein promotes phagocyte resistance and systemic virulence. FASEB J. 22: 1715-1724 [Abstract] [Full Text]  
• Jones, A. L., Mertz, R. H., Carl, D. J., Rubens, C. E. (2007). A Streptococcal Penicillin-Binding Protein Is Critical for Resisting Innate Airway Defenses in the Neonatal Lung. J. Immunol. 179: 3196-3202 [Abstract] [Full Text]  
• Meehl, M., Herbert, S., Gotz, F., Cheung, A. (2007). Interaction of the GraRS Two-Component System with the VraFG ABC Transporter To Support Vancomycin-Intermediate Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 51: 2679-2689 [Abstract] [Full Text]