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This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-093963v1 22/6/1715    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Maisey, H. C. Articles by Doran, K. S. PubMed PubMed Citation Articles by Maisey, H. C. Articles by Doran, K. S.

A group B streptococcal pilus protein promotes phagocyte resistance and systemic virulence

Heather C. Maisey^*, Darin Quach, Mary E. Hensler^*, George Y. Liu^||, Richard L. Gallo, Victor Nizet^*, and Kelly S. Doran^*,,1

^* Department of Pediatrics, Division of Pharmacology and Drug Discovery,

Department of Medicine, Division of Dermatology, and

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, School of Medicine, La Jolla, California, USA;

Department of Biology and Center for Microbial Sciences, San Diego State University, San Diego, California, USA; and

^|| Division of Pediatric Infectious Diseases and the Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

¹Correspondence: San Diego State University, Life Sciences North, Rm. 317, 5500 Campanile Dr., San Diego, CA 92182-4614, USA. E-mail: kdoran{at}sciences.sdsu.edu

Group B Streptococcus (GBS) is a major cause of invasive bacterial infections in newborns and certain adult populations. Surface filamentous appendages known as pili have been recently identified in GBS. However, little is known about the role of these structures in disease pathogenesis. In this study we sought to probe potential functional role(s) of PilB, the major GBS pilus protein subunit, by coupling analysis of an isogenic GBS pilB knockout strain with heterologous expression of the pilB gene in the nonpathogenic bacterium Lactococcus lactis. We found the knockout GBS strain that lacked PilB was more susceptible than wild-type (WT) GBS to killing by isolated macrophages and neutrophils. Survival was linked to the ability of PilB to mediate GBS resistance to cathelicidin antimicrobial peptides. Furthermore, the PilB-deficient GBS mutant was more readily cleared from the mouse bloodstream and less-virulent in vivo compared to the WT parent strain. Strikingly, overexpression of the pilB gene alone in L. lactis enhanced resistance to phagocyte killing, increased bloodstream survival, and conferred virulence in a mouse challenge model. Together these data demonstrate that the pilus backbone subunit, PilB, plays an integral role in GBS virulence and suggests a novel role for gram-positive pili in thwarting the innate defenses of phagocyte killing.—Maisey, H.C., Quach, D., Hensler, M. E., Liu, G. Y., Gallo, R. L., Nizet, V., Doran, K. S. A group B streptococcal pilus protein promotes phagocyte resistance and systemic virulence.

Key Words: Streptococcus agalactiae • pili • GBS • macrophage • neutrophil • antimicrobial peptides

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				J. W. Rosch, B. Mann, J. Thornton, J. Sublett, and E. Tuomanen Convergence of Regulatory Networks on the Pilus Locus of Streptococcus pneumoniae Infect. Immun., July 1, 2008; 76(7): 3187 - 3196. [Abstract] [Full Text] [PDF]