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.

The Human Intestinal Microbiota

Special issue: The Human Intestinal Microbiota

Harry J. Flint¹, Paul W. O'Toole² and Alan W. Walker^3
1 Microbial Ecology Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Bucksburn, Aberdeen AB21 9SB, UK
² Department of Microbiology and the Alimentary Pharmabiotic Centre, University College Cork, Ireland
³ Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK

Correspondence
Harry J. Flint
h.flint@rowett.ac.uk
The human intestine is home to very large numbers of micro-organisms, with bacterial cells exceeding 10¹¹ ml^–1 in the colon. The impact that this complex community has upon the host is increasingly recognized not only as a potential source of infection but also as a contributor to nutrient and energy supply, gut development and immune homeostasis. Recent evidence has indicated links between gut microbial activities and the aetiology of disorders such as inflammatory bowel disease and colorectal cancer, and also conditions such as heart disease, diabetes and metabolic syndrome. All this makes a special issue of Microbiology devoted to the human intestinal microbiota timely. This topic necessarily depends heavily on microbial ecology, a discipline that has not always been natural territory for the journal, notwithstanding some important contributions to human intestinal microbiology (e.g. Macfarlane et al., 1986). Molecular methodologies have done much to accelerate recent progress by allowing the rapid analysis of this complex community, culminating in the application of in-depth metagenomics (Qin et al., 2010). Nevertheless, the commonly perceived wisdom that most human intestinal bacteria are inherently unculturable may not be entirely accurate, since many of the most common intestinal bacteria found by molecular methods in faecal samples correspond to cultured species of obligate anaerobes (Walker et al., 2010). The future, in which the journal can play an important role, will surely require a combination of genomics, microbial ecology and studies of single cultured organisms.
Four reviews in this special issue deal with the role of the human gut microbiota in irritable bowel syndrome (Salonen et al., 2010), the metabolism of dietary phytochemicals (Kemperman et al., 2010), interactions of probiotic bacteria with the gut mucosa (Sánchez et al., 2010) and the impact of long-term antibiotic use on the gut microbial community (Jernberg et al., 2010). The impact of a new antibiotic upon the intestinal community of Clostridium difficile-infected patients is reported by Tannock et al. (2010). The diversity of the intestinal community is explored by Roger & McCartney (2010) and by Roger et al. (2010) in infants, by Rajili-Stojanovi et al. (2010) in an in vitro intestinal model system and by Contreras et al. (2010) in the oral cavity of Amerindians. Interactions of intestinal bacteria with the mammalian immune system are considered by Knoch et al. (2010) for the microbial community of the caeca of interleukin-10 gene-deficient mice, and by Donato et al. (2010) for a probiotic strain of Lactobacillus rhamnosus. Probiotic and prebiotic approaches are of course aimed at manipulating the intestinal microbial community and host responses to achieve health benefits. Penders et al. (2010) explore the possible relationship between lactobacilli and allergy, while O'Flaherty & Klaenhammer (2010) report on a Lactobacillus acidophilus surface protein, and MacKenzie et al. (2010) on mucin-binding proteins of Lactobacillus reuteri. Bifidobacteria are most commonly chosen as targets for prebiotics, and understanding of this group is advanced by a comparative genomic study by Bottacini et al. (2010). An informative study using an in vitro fermenter model (Zihler et al., 2010), however, illustrates the difficulty of predicting the impact of prebiotics and probiotics on complex microbial communities. Finally, one paper focuses on an obligate anaerobe, examining the capsular polysaccharides of Bacteroides fragilis (Patrick et al., 2010).
We would like to thank all the authors who responded to the call for manuscripts to be considered for this special issue, and to all the reviewers and editors involved in processing these papers. This has resulted in a valuable and varied set of contributions that provide a snapshot of the rapid progress taking place in this topical field. We firmly believe that Microbiology can make an increasingly valuable contribution to this field in the future by publishing quality papers on the ecology, physiology and genetics of micro-organisms that inhabit the human intestinal tract.

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