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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Secuenciación del genoma de Rhodococcus equi.

El primer firmante del trabajo hizo su Tesis Doctoral en nuestro grupo de investigacion de la ULE

The Genome of a Pathogenic Rhodococcus: Cooptive Virulence Underpinned by Key Gene Acquisitions

Michal Letek¹, Patricia González^1,2, Iain MacArthur^1,2,3, Héctor Rodríguez^1,2, Tom C. Freeman⁴, Ana Valero-Rello^1,2, Mónica Blanco^1,2, Tom Buckley², Inna Cherevach⁵, Ruth Fahey⁶, Alexia Hapeshi¹, Jolyon Holdstock⁷, Desmond Leadon², Jesús Navas⁸, Alain Ocampo², Michael A. Quail⁵, Mandy Sanders⁵, Mariela M. Scortti^1,9, John F. Prescott³, Ursula Fogarty², Wim G. Meijer⁶, Julian Parkhill⁵, Stephen D. Bentley⁵, José A. Vázquez-Boland^1,10*

We report the genome of the facultative intracellular parasite Rhodococcus equi, the only animal pathogen within the biotechnologically important actinobacterial genus Rhodococcus. The 5.0-Mb R. equi 103S genome is significantly smaller than those of environmental rhodococci. This is due to genome expansion in nonpathogenic species, via a linear gain of paralogous genes and an accelerated genetic flux, rather than reductive evolution in R. equi. The 103S genome lacks the extensive catabolic and secondary metabolic complement of environmental rhodococci, and it displays unique adaptations for host colonization and competition in the short-chain fatty acid–rich intestine and manure of herbivores—two main R. equi reservoirs. Except for a few horizontally acquired (HGT) pathogenicity loci, including a cytoadhesive pilus determinant (rpl) and the virulence plasmid vap pathogenicity island (PAI) required for intramacrophage survival, most of the potential virulence-associated genes identified in R. equi are conserved in environmental rhodococci or have homologs in nonpathogenic Actinobacteria. This suggests a mechanism of virulence evolution based on the cooption of existing core actinobacterial traits, triggered by key host niche–adaptive HGT events. We tested this hypothesis by investigating R. equi virulence plasmid-chromosome crosstalk, by global transcription profiling and expression network analysis. Two chromosomal genes conserved in environmental rhodococci, encoding putative chorismate mutase and anthranilate synthase enzymes involved in aromatic amino acid biosynthesis, were strongly coregulated with vap PAI virulence genes and required for optimal proliferation in macrophages. The regulatory integration of chromosomal metabolic genes under the control of the HGT–acquired plasmid PAI is thus an important element in the cooptive virulence of R. equi.
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1001145

Los Premios Nobeles también se equivocan.......

Two prominent journals have retracted papers by Nobel laureate Linda Buck today because she was "unable to reproduce [the] key findings" of experiments done by her former postdoctoral researcher Zhihua Zou, according to a statement made by the Fred Hutchinson Cancer Research Center (FHCRC), where Buck worked at the time of the publications.

These retractions, a 2006 Science paper and a 2005 Proceedings of the National Academy of the Sciences (PNAS) paper, are tied to a 2001 Nature paper that she retracted in 2008, due to the inability "to reproduce the reported findings" and "inconsistencies between some of the figures and data published in the paper and the original data," according to the retraction. Zou was the first author on all three papers and responsible for conducting the experiments.

The FHCRC is currently conducting an investigation into the issue, said Kristen Woodward, senior media relations manager, but no findings of misconduct have been made. John Dahlberg of the Office of Research Integrity declined to comment on the matter.

The paper in PNAS, which has been cited 61 times according to ISI, describes how smells from substances with similar molecular structures elicit "strikingly similar" neuronal patterns in the olfactory cortex of mice brains across individuals, supporting the presence of "olfactory maps" that follow "an underlying logic," according to the paper. The Science paper, cited 73 times, furthers the research and supports that mixed smells, such as chocolate and citrus, activate neurons in the olfactory cortex that chocolate or citrus do not when presented individually, which may explain why these mixtures tend to smell like completely different substances to humans.

Fortunately, the retractions will not have a large impact on the field, Donald Wilson, an olfactory researcher at New York University and Nathan Kline Institute, told The Scientist in an email. "The story of how cortical odor processing occurs doesn't change," he said. "Work in our own lab and others have now also shown the highly distributed, sparse nature of odor processing in the olfactory cortex, and the complex processes involved in dealing with odor mixtures, much as these two now retracted papers showed."

Zou was unavailable for comment, as his current location is unknown, according to FHCRC. After completing his post doctoral research with Buck at FHCRC in 2005, Zou took an assistant professor position at the University of Texas Medical Branch (UTMB) in Galveston. In November of 2008, however, Zou was laid off from the institution, along with 2,400 other UTMB staff members, after Hurricane Ike ripped the university apart that September, according to Raul Reyes, the director of media relations at the UTMB.

In 2008, Zou wrote in a statement provided by UTMB that he was "disappointed" by the Nature retraction, and denied any misconduct on his part. While Zou agreed to the Nature retraction, he "declined to sign" the Science retraction, as reported online today in Science. But "we have no information to suspect misconduct," Natasha Pinol, senior communications officer at the AAAS/Science Office of Public Programs, told The Scientist in an email.

In addition to the irreproducible results, the PNAS paper also contained "figures inconsistent with original data," according to the FHCRC statement. While the PNAS retraction is "not embargoed," according to Managing Editor Daniel Salsbury, the journal refused to share any information with The Scientist before deadline, noting that the retraction would appear online after 2:00 p.m. EDT this afternoon.

The research that won Buck the 2004 Nobel Prize, which she shared with olfactory researcher Richard Axel of Columbia University "for their discoveries of odorant receptors and the organization of the olfactory system," was unrelated to the research in the retracted papers.

Un nuevo caso de terapia génica

Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia.

 

Disorders caused by abnormal [beta]-globin, such as

[beta]-thalassaemia, are the most prevalent inherited disorders

worldwide. For treatment, many patients are dependent on blood

transfusions; thus far the only cure has involved matched

transplantation of haematopoietic stem cells. Here it is shown that

lentiviral [beta]-globin gene transfer can be an effective substitute

for regular transfusions in a patient with severe [beta]-thalassaemia

 

http://www.nature.com/nature/journal/v467/n7313/abs/nature09328.html

Nature, septiembre del 2010

Virus gigantes o giruses

DNA Viruses: The Really Big Ones (Giruses)

Annual Review of Microbiology

Vol. 64: 83-99 (Volume publication date October 2010)

First published online as a Review in Advance on May 12, 2010

James L. Van Etten,^1,2 Leslie C. Lane,¹ and David D. Dunigan^1,2

¹Department of Plant Pathology, University of Nebraska, Lincoln, Nebraska 68583;

²Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska 68583; email: jvanetten@unlnotes.unl.edu

 

Viruses with genomes greater than 300 kb and up to 1200 kb are being discovered with increasing frequency. These large viruses (often called giruses) can encode up to 900 proteins and also many tRNAs. Consequently, these viruses have more protein-encoding genes than many bacteria, and the concept of small particle/small genome that once defined viruses is no longer valid. Giruses infect bacteria and animals although most of the recently discovered ones infect protists. Thus, genome gigantism is not restricted to a specific host or phylogenetic clade. To date, most of the giruses are associated with aqueous environments. Many of these large viruses (phycodnaviruses and Mimiviruses) probably have a common evolutionary ancestor with the poxviruses, iridoviruses, asfarviruses, ascoviruses, and a recently discovered Marseillevirus. One issue that is perhaps not appreciated by the microbiology community is that large viruses, even ones classified in the same family, can differ significantly in morphology, lifestyle, and genome structure. This review focuses on some of these differences than on extensive details about individual viruses.

A bizarre, humped Carcharodontosauria (Theropoda) from the Lower Cretaceous of Spain

Carcharodontosaurs were the largest predatory dinosaurs, and their early evolutionary history seems to be more intricate than was previously thought. Until recently, carcharodontosaurs were restricted to a group of large theropods inhabiting the Late Cretaceous Gondwanan land masses^{1, 2}, but in the last few years Laurasian evidence^{3, 4, 5} has been causing a reevaluation of their initial diversification⁶. Here we describe an almost complete and exquisitely preserved skeleton of a medium-sized (roughly six metres long) theropod from the Lower Cretaceous series (Barremian stage) Konservat-Lagerstätte of Las Hoyas⁷ in Cuenca, Spain. Cladistic analysis supports the idea that the new taxon Concavenator corcovatus is a primitive member of Carcharodontosauria⁶, exhibiting two unusual features: elongation of the neurapophyses of two presacral vertebrae forming a pointed, hump-like structure and a series of small bumps on the ulna. We think that these bumps are homologous to quill knobs present on some modern birds; the knobs are related to the insertion area of follicular ligaments that anchor the roots of the flight feathers (remiges) to the arm. We propose that Concavenator has integumentary follicular structures inserted on the ulna, as in modern birds. Because scales do not have follicles, we consider the structures anchored to the Concavenator arms to be non-scale skin appendages homologous to the feathers of modern birds. If this is true, then the phylogenetic bracket for the presence of non-scale skin structures homologous to feathers in theropod dinosaurs would be extended to the Neotetanurae, enlarging the scope for explaining the origin of feathers in theropods.

http://links.ealert.nature.com/ctt?kn=248&m=35773183&r=MjA1NzUwMTcwNgS2&b=2&j=ODE0MTc3MTES1&mt=1&rt=0