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Journal of Bacteriology, April 2008, p. 2257-2265, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01545-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Staphylococcus aureus CodY Negatively Regulates Virulence Gene Expression{triangledown}

Charlotte D. Majerczyk,1 Marat R. Sadykov,2 Thanh T. Luong,3 Chia Lee,3 Greg A. Somerville,2 and Abraham L. Sonenshein1,4*

Tufts University Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts 02111,1 University of Nebraska, Lincoln, Nebraska 68583,2 University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205,3 Tufts University School of Medicine, Boston, Massachusetts 021114

Received 25 September 2007/ Accepted 13 December 2007

CodY is a global regulatory protein that was first discovered in Bacillus subtilis, where it couples gene expression to changes in the pools of critical metabolites through its activation by GTP and branched-chain amino acids. Homologs of CodY can be found encoded in the genomes of nearly all low-G+C gram-positive bacteria, including Staphylococcus aureus. The introduction of a codY-null mutation into two S. aureus clinical isolates, SA564 and UAMS-1, through allelic replacement, resulted in the overexpression of several virulence genes. The mutant strains had higher levels of hemolytic activity toward rabbit erythrocytes in their culture fluid, produced more polysaccharide intercellular adhesin (PIA), and formed more robust biofilms than did their isogenic parent strains. These phenotypes were associated with derepressed levels of RNA for the hemolytic alpha-toxin (hla), the accessory gene regulator (agr) (RNAII and RNAIII/hld), and the operon responsible for the production of PIA (icaADBC). These data suggest that CodY represses, either directly or indirectly, the synthesis of a number of virulence factors of S. aureus.

* Corresponding author. Mailing address: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-6761. Fax: (617) 636-0337. E-mail: linc.sonenshein{at}tufts.edu

{triangledown} Published ahead of print on 21 December 2007.

Journal of Bacteriology, April 2008, p. 2257-2265, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01545-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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