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Journal of Bacteriology, December 2004, p. 8463-8471, Vol. 186, No. 24
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.24.8463-8471.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Revising the Role of the Pneumococcal vex-vncRS Locus in Vancomycin Tolerance

Wolfgang Haas,1,{dagger} Jack Sublett,1 Deepak Kaushal,2 and Elaine I. Tuomanen1*

Department of Infectious Diseases,1 Functional Genomics, Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee2

Received 14 June 2004/ Accepted 9 September 2004

Vancomycin is used increasingly to treat invasive infections caused by multidrug-resistant Streptococcus pneumoniae. Although no vancomycin-resistant strains have been isolated to date, tolerant strains that fail to die rapidly and that cause relapsing disease have been described. The vex123-pep27-vncRS locus, consisting of an ABC transporter, a presumed signaling peptide, and a two-component system, respectively, has been implicated in vancomycin tolerance. Recent findings, however, challenged this model. The data presented here indicate that erythromycin in the growth medium induces a vancomycin-tolerant phenotype and that loss of function of Pep27 or VncRS does not alter autolysis. However, a role for the ABC transporter encoded by the vex123 genes in tolerance was confirmed. A vex3 mutant was considerably more tolerant to vancomycin treatment than the wild-type strain T4, and the strength of the phenotype depended on the orientation of the resistance cassette used to construct the mutant. Microarray results suggested a number of genes that might be involved in tolerance in the vex3 mutant. Although the exact function and regulation of the vex123-pep27-vncRS locus remains to be determined, several factors influence the autolysis behavior of S. pneumoniae, including the bacterial capsule, erythromycin, and the lytA and vex3 gene products.

* Corresponding author. Mailing address: Department of Infectious Diseases, 332 N. Lauderdale St., Memphis, TN 38105. Phone: (901) 495-3114. Fax: (901) 495-3099. E-mail: elaine.tuomanen{at}stjude.org.

{dagger} Present address: Department of Microbiology and Immunology, School of Medicine and Dentistry, Rochester, NY 14642.

Journal of Bacteriology, December 2004, p. 8463-8471, Vol. 186, No. 24
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.24.8463-8471.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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