Ácidos teicoicos como reguladores del entrecruzamiento de peptidoglucano

Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus

1. Magda L. Atilano^a,¹,
2. Pedro M. Pereira^b,¹,
3. James Yates^a,
4. Patricia Reed^b,
5. Helena Veiga^b,
6. Mariana G. Pinho^b,²,³, and
7. Sérgio R. Filipe^a,²,³

+ Author Affiliations

1. ^aLaboratory of Bacterial Cell Surfaces and Pathogenesis and
2. ^bLaboratory of Bacterial Cell Biology, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, 2781-901 Oeiras, Portugal

1. Edited by Richard P. Novick, New York University School of Medicine, New York, New York, and approved September 20, 2010 (received for review April 1, 2010)
2. ↵¹M.L.A. and P.M.P. contributed equally to this work.
3. ↵²M.G.P. and S.R.F. contributed equally to this work.

Abstract

The cell wall of Staphylococcus aureus is characterized by an extremely high degree of cross-linking within its peptidoglycan (PGN). Penicillin-binding protein 4 (PBP4) is required for the synthesis of this highly cross-linked peptidoglycan. We found that wall teichoic acids, glycopolymers attached to the peptidoglycan and important for virulence in Gram-positive bacteria, act as temporal and spatial regulators of PGN metabolism, controlling the level of cross-linking by regulating PBP4 localization. PBP4 normally localizes at the division septum, but in the absence of wall teichoic acids synthesis, it becomes dispersed throughout the entire cell membrane and is unable to function normally. As a consequence, the peptidoglycan of TagO null mutants, impaired in wall teichoic acid biosynthesis, has a decreased degree of cross-linking, which renders it more susceptible to the action of lysozyme, an enzyme produced by different host organisms as an initial defense against bacterial infection.

• cell division
• cell wall
• penicillin-binding proteins
• transpeptidases
• lysozyme

Footnotes

• ³To whom correspondence may be addressed. E-mail: mgpinho@itqb.unl.pt or sfilipe@itqb.unl.pt.
• Author contributions: M.L.A., P.M.P., M.G.P., and S.R.F. designed research; M.L.A., P.M.P., J.Y., and P.R. performed research; M.L.A., P.M.P., M.G.P., and S.R.F. analyzed data; H.V. contributed new reagents/analytic tools; and M.L.A., P.M.P., M.G.P., and S.R.F. wrote the paper.
• The authors declare no conflict of interest.
• This article is a PNAS Direct Submission.
• This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1004304107/-/DCSupplemental.

Freely available online through the PNAS open access option.