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Infection and Immunity, October 2002, p. 5428-5437, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5428-5437.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Increased Expression of Clumping Factor and Fibronectin-Binding Proteins by hemB Mutants of Staphylococcus aureus Expressing Small Colony Variant Phenotypes

Pierre Vaudaux,1* Patrice Francois,1 Carmelo Bisognano,1 William L. Kelley,1 Daniel P. Lew,1 Jacques Schrenzel,1 Richard A. Proctor,2 Peter J. McNamara,2 G. Peters,3 and Christof Von Eiff3

Division of Infectious Diseases, University Hospital, CH-1211 Geneva 14, Switzerland,1 Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin,2 and Institute of Medical Microbiology, University of Münster, Münster, Germany3

Received 14 December 2001/ Returned for modification 26 March 2002/ Accepted 1 July 2002

Small colony variants (SCVs) of Staphylococcus aureus are slow-growing subpopulations that cause persistent and relapsing infections. The altered phenotype of SCV can arise from defects in menadione or hemin biosynthesis, which disrupt the electron transport chain and decrease ATP concentrations. With SCVs, virulence is altered by a decrease in exotoxin production and susceptibility to various antibiotics, allowing their intracellular survival. The expression of bacterial adhesins by SCVs is poorly documented. We tested fibrinogen- and fibronectin-mediated adhesion of a hemB mutant of S. aureus 8325-4 that is defective for hemin biosynthesis and exhibits a complete SCV phenotype. In this strain, adhesion to fibrinogen and fibronectin was significantly higher than that of its isogenic, normally growing parent and correlated with the increased surface display of these adhesins as assessed by flow cytometry. Real-time quantitative reverse transcription-PCR demonstrated increased expression of clfA and fnb genes by the hemB mutant compared to its isogenic parent. The influence of the hemB mutation on altered adhesin expression was confirmed by showing complete restoration of the wild-type adhesive phenotype in the hemB mutant, either by complementing with intact hemB or by supplementing the growth medium with hemin. Increased surface display of fibrinogen and fibronectin adhesins by the hemB mutation occurred independently from agr, a major regulatory locus of virulence factors in S. aureus. Both agr-positive and agr-lacking hemB mutants were also more efficiently internalized by human embryonic kidney cells than were their isogenic controls, presumably because of increased surface display of their fibronectin adhesins.

* Corresponding author. Mailing address: Division of Infectious Diseases, University Hospital, CH 1211 Geneva 14, Switzerland. Phone: (4122) 37 29 826. Fax: (4122) 37 29 830. E-mail: Pierre.vaudaux{at}hcuge.ch.

Editor: V. J. DiRita

Infection and Immunity, October 2002, p. 5428-5437, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5428-5437.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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