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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Donato, K. A., Gareau, M. G., Wang, Y. J. J. & Sherman, P. M. (2010). Lactobacillus rhamnosus GG attenuates interferon- and tumor necrosis factor--induced barrier dysfunction and pro-inflammatory signalling. Microbiology 156, 3288–3297.[Abstract/Free Full Text]
Jernberg, C., Löfmark, S., Edlund, C. & Jansson, J. (2010). Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 156, 3216–3223.[Abstract/Free Full Text]
Kemperman, R. A., Bolca, S., Roger, L. C. & Vaughan, E. E. (2010). Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities. Microbiology 156, 3224–3231.[Abstract/Free Full Text]
Knoch, B., Nones, K., Barnett, M. P. G., McNabb, W. C. & Roy, N. C. (2010). Diversity of cecal bacteria is altered in interleukin-10 gene-deficient mice before and after colitis onset and when fed polyunsaturated fatty acids. Microbiology 156, 3306–3316.[Abstract/Free Full Text]
Macfarlane, G. T., Cummings, J. H. & Allison, C. (1986). Protein degradation by human intestinal bacteria. J Gen Microbiol 132, 1647–1656.[Abstract/Free Full Text]
MacKenzie, D. A., Jeffers, F., Parker, M. L., Vibert-Vallet, A., Bongaerts, R. J., Roos, S., Walter, J. & Juge, N. (2010). Strain-specific diversity of mucus-binding proteins in the adhesion and aggregation properties of Lactobacillus reuteri. Microbiology 156, 3368–3378.[Abstract/Free Full Text]
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Patrick, S., Blakely, G. W., Houston, S., Moore, J., Abratt, V. R., Bertalan, M., Cerdeño-Tárraga, A. M., Quail, M. A., Corton, N. & other authors (2010). Twenty-eight divergent polysaccharide loci specifying within- and amongst-strain capsule diversity in three strains of Bacteroides fragilis. Microbiology 156, 3255–3269.[Abstract/Free Full Text]
Penders, J., Thijs, C., Mommers, M., Stobberingh, E. E., Dompeling, E., Reijmerink, N. E., van den Brandt, P. A., Kerkhof, M., Koppelman, G. H. & Postma, D. S. (2010). Intestinal lactobacilli and the DC-SIGN gene for their recognition by dendritic cells play a role in the aetiology of allergic manifestations. Microbiology 156, 3298–3305.[Abstract/Free Full Text]
Qin, J. J., Li, R. Q., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F. & other authors (2010). A human gut microbial gene catalogue established by metagenome sequencing. Nature 464, 59–65.[CrossRef][Medline]
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Tannock, G. W., Munro, K., Taylor, C., Lawley, B., Young, W., Byrne, B., Emery, J. & Louie, T. (2010). A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin. Microbiology 156, 3354–3359.[Abstract/Free Full Text]
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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

Estructura del genoma del pueblo judio

Nature advance online publication 9 June 2010 | doi:10.1038/nature09103; Received 9 December 2009; Accepted 21 April 2010; Published online 9 June 2010

The genome-wide structure of the Jewish people

Doron M. Behar^1,2,14, Bayazit Yunusbayev^2,3,14, Mait Metspalu^2,14, Ene Metspalu², Saharon Rosset⁴, Jüri Parik², Siiri Rootsi², Gyaneshwer Chaubey², Ildus Kutuev^2,3, Guennady Yudkovsky^1,5, Elza K. Khusnutdinova³, Oleg Balanovsky⁶, Ornella Semino⁷, Luisa Pereira^8,9, David Comas¹⁰, David Gurwitz¹¹, Batsheva Bonne-Tamir¹¹, Tudor Parfitt¹², Michael F. Hammer¹³, Karl Skorecki^1,5 & Richard Villems²

1. Molecular Medicine Laboratory, Rambam Health Care Campus, Haifa 31096, Israel
2. Estonian Biocentre and Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia
3. Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa 450054, Russia
4. Department of Statistics and Operations Research, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel
5. Rappaport Faculty of Medicine and Research Institute, Technion – Israel Institute of Technology, Haifa 31096, Israel
6. Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow 115478, Russia
7. Dipartimento di Genetica e Microbiologia, Università di Pavia, Pavia 27100, Italy
8. Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto 4200-465, Portugal
9. Faculdade de Medicina, Universidade do Porto, Porto 4200-319, Portugal
10. Institute of Evolutionary Biology (CSIC-UPF), CEXS-UPF-PRBB and CIBER de Epidemiología y Salud Pública, Barcelona 08003, Spain
11. Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
12. Department of the Languages and Cultures of the Near and Middle East, Faculty of Languages and Cultures, School of Oriental and African Studies (SOAS), University of London, London WC1H 0XG, UK
13. ARL Division of Biotechnology, University of Arizona, Tucson, Arizona 85721, USA
14. These authors contributed equally to this work.

Correspondence to: Doron M. Behar^1,2,14 Email: behardm@usernet.com

Correspondence to: Karl Skorecki^1,5 Email: skorecki@tx.technion.ac.il

Correspondence to: Richard Villems² Email: rvillems@ebc.ee

Top of page

Abstract

Contemporary Jews comprise an aggregate of ethno-religious communities whose worldwide members identify with each other through various shared religious, historical and cultural traditions^{1, 2}. Historical evidence suggests common origins in the Middle East, followed by migrations leading to the establishment of communities of Jews in Europe, Africa and Asia, in what is termed the Jewish Diaspora^{3, 4, 5}. This complex demographic history imposes special challenges in attempting to address the genetic structure of the Jewish people⁶. Although many genetic studies have shed light on Jewish origins and on diseases prevalent among Jewish communities, including studies focusing on uniparentally and biparentally inherited markers^{7, 8, 9, 10, 11, 12, 13, 14, 15, 16}, genome-wide patterns of variation across the vast geographic span of Jewish Diaspora communities and their respective neighbours have yet to be addressed. Here we use high-density bead arrays to genotype individuals from 14 Jewish Diaspora communities and compare these patterns of genome-wide diversity with those from 69 Old World non-Jewish populations, of which 25 have not previously been reported. These samples were carefully chosen to provide comprehensive comparisons between Jewish and non-Jewish populations in the Diaspora, as well as with non-Jewish populations from the Middle East and north Africa. Principal component and structure-like analyses identify previously unrecognized genetic substructure within the Middle East. Most Jewish samples form a remarkably tight subcluster that overlies Druze and Cypriot samples but not samples from other Levantine populations or paired Diaspora host populations. In contrast, Ethiopian Jews (Beta Israel) and Indian Jews (Bene Israel and Cochini) cluster with neighbouring autochthonous populations in Ethiopia and western India, respectively, despite a clear paternal link between the Bene Israel and the Levant. These results cast light on the variegated genetic architecture of the Middle East, and trace the origins of most Jewish Diaspora communities to the Levant.

Microbiota vaginal (Tomado del Blog de Manuel Sanchez)

Una colaboración entre varios grupos investigadores ha llevado a cabo un estudio para entender el microbioma vaginal humano y su papel en la defensa frente a las infecciones urogenitales femeninas. Para ello han tomado muestras de la microbiota vaginal de 396 mujeres norteamericanas pertenecientes a cuatro grupos étnicos: blancas, negras, hispanas, y asiáticas. La microbiota fue analizada mediante diversos procedimientos incluyendo la secuenciación y comparación de los genes que codifican para el 16S rRNA. Los resultados han sido publicados en la revista PNAS.

Uno de los objetivos era determinar si había un "microbioma nuclear" (core microbiome) común a la microbiota vaginal de todas las mujeres. Algo similar a lo que se ha descrito para la microbiota intestinal o para la del pene. Pero no ha sido así. Han encontrado que la microbiota vaginal presenta una diversidad de comunidades bacterianas que se pueden agrupar en cinco grupos (clusters). Los grupos I, II, III y V están dominados por las especies Lactobacillus crispatus, L. gasseri, L. iners, y L. jensenii. El grupo IV es muy diverso y tiene una alta proporción de organimos estrictamente anaerobios. Pero lo más importante es que los cinco grupos bacterianos tienen en común la producción de ácido láctico, un compuesto clave en la ecología de la microbiota vaginal. Es decir, no hay un "microbioma nuclear" pero las diversas comunidades microbianas interactúan como si lo hubiera. El láctico es el responsable de que el pH vaginal sea ácido, creando unas condiciones en el que no pueden crecer numerosos microorganismos patógenos.

Esquema que muestra los cinco agrupamientos genéticos (I al V) encontrados en la microbiota vaginal. La cantidad de ramas nos indica la diversidad microbiana. En la parte de abajo tenemos los valores Nugent para los distintos microorganismos caracterizados. El color rojo indica que esos micrroganismos pueden participar en procesos de vaginosisi aunque se encuentren en la microbiota normal. En la barra más inferior se indica el valor de pH óptimo de dichos microorganismos. (fuente: Ravel et al.)

Sin embargo, no todas las comunidades microbianas que forman la microbiota vaginal son igual de protectoras frente a los patógenos externos. Es importante que haya un equilibrio dinámico entre ellas para mantener una correcta salud vaginal. Las muestras vaginales fueron sometidas a los llamados criterios o puntuación de Nugent para el diagnóstico de la vaginosis bacteriana. Se realiza una tinción de Gram y se evalúa al microscopio la presencia de bacilos grandes Gram-positivos que corresponde a los Lactobacillus. Como esas bacterias corresponden a la flora normal el valor 0 se da cuando hay muchas y el valor 4 cuando hay pocas. Luego se cuentan los bacilos pequeños Gram-variables que suelen corresponder al patógeno Gardenella vaginalis, pero en este caso el 0 es para cuando no se ve ninguna y el 4 para muchas. Y finalmente se evalúan los bacilos curvados Gram-variable que se corresponden con el morfotipo patógeno Mobiluncus, aunque los valores se dan entre 0 y 2. Una puntuación de 7 ó más ese considera como indicadora de una vaginosis bacteriana. Al correlacionar los resultados genéticos con los resultados obtenidos tras aplicar el criterio de Nugent lo que se ha encontrado es que la mayor parte de microorganismos del grupo IV tienen valores de Nugent altos, mientras que los del grupo I presentan los valores más bajos.

Un resultado llamativo ha sido encontrar que hay diferencias entre los diferentes grupos étnicos. Las mujeres hispanoamericanas tienen el pH más alto (pH 5.0 ± 0.59), seguidas de las mujeres negras (pH 4.7 ± 1.04), las asiáticas (pH 4.4 ± 0.59) y finalmente las mujeres blancas (pH 4.2 ± 0.3). Esos datos se correlacionan con el hecho de que las comunidades microbianas dominadas por los lactobacilos son más abundantes en las mujeres blancas y asiáticas. Paralelamente, las comunidades microbianas que no ofrecen una protección óptima frente a los patógenos eran más comunes en las mujeres hispanoamericanas y negras que en las asiáticas y blancas.

Representación de la distribución de las comunidades bacterianas vaginales por grupo étnico. Entre paréntesis se muestra el número de mujeres muestreadas en cada grupo étnico. (fuente Ravel et al.)

El porqué de dichas diferencias es desconocido. Pero los autores dejan muy claro en el artículo que esto no quiere decir que la microbiota vaginal de las mujeres blancas y asiáticas sea más "saludable" que la de las mujeres negras e hispanas porque todas las muestras fueron recogidas de mujeres sanas. Por trabajos anteriores se sabe que la composición de la microbiota vaginal depende de factores muy diversos debidos al hospedador como son: el funcionamiento del sistema inmune, ya sea el innato o el adaptativo, las secreciones vaginales, las células del epitelio, los hábitos de higiene, los métodos anticonceptivos y el comportamiento sexual.

Como indican al final del artículo, las diferencias en la composición de las comunidades bacterianas vaginales deben de ser tomadas en cuenta cuando se estiman los riesgos de padecer una enfermedad, o bien para su diagnosis y tratamiento. Estos trabajos son los primeros pasos hacia la creación de una medicina personalizada enfocada hacia la salud reproductora de la mujer.

Nugent RP, Krohn MA, & Hillier SL (1991). Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. Journal of clinical microbiology, 29 (2), 297-301 PMID: 1706728

Ravel, J., Gajer, P., Abdo, Z., Schneider, G., Koenig, S., McCulle, S., Karlebach, S., Gorle, R., Russell, J., Tacket, C., Brotman, R., Davis, C., Ault, K., Peralta, L., & Forney, L. (2010). Microbes and Health Sackler Colloquium: Vaginal microbiome of reproductive-age women Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1002611107

Amor de madre

Aunque mañana sea el día del Padre, la siguiente entrada está basada en el comentario "Mother's Love" escrito por Moselio Schaechter en su blog "Small Things Considered".

La fisión binaria es una invención impresionante. De un solo golpe, asegura que las células descendientes nazcan iguales y dotadas del mismo potencial para el crecimiento y la supervivencia. Tan simple como suena, deben de haberse requerido unas considerables contorsiones evolutivas para que funcione tan bien en todo el mundo viviente.

En la fisión binaria se replica el material genético (en rojo) y se duplica el contenido celular. Tras la división celular las dos células resultantes son idénticas

Sin embargo, hay células que han adoptado un mecanismo alternativo, en el cual la división celular es asimétrica, donde la célula naciente es originada a partir de una "célula madre" que posteriormente generará más "bebés". El ejemplo más conocido es, por supuesto, el proceso de gemación en las levaduras. Hay otras células que también se reproducen de esa manera, incluyendo algunas bacterias, las esporas sexuales de las setas, e incluso algunas células de plantas.

En la gemación se replica el material genético pero no se duplica el contenido celular. Se produce una yema o gema a partir de la célula madre. Tras la división celular hay dos células desiguales. En la célula madre se produce una cicatriz en su superficie y podrá repetir el proceso hasta unas 30 veces, después de los cuales muere. La célula hija, también denominada "célula virgen", debe de crecer antes de convertirse en una célula madre con capacidad reproductora

Por lo tanto, ¿hay alguna ventaja para abandonar la fisión binaria y realizar la gemación en su lugar? Podría ser así. Los últimos trabajos del laboratorio de Tom Nyström han demostrado que las proteínas que se dañan durante el crecimiento celular, fluyen hacia la célula madre y así dejan a la joven nueva célula libre de tales impedimentos. El daño a las proteínas es a menudo debido a la oxidación causada por especies reactivas de oxígeno. Las proteínas dañadas tienden a formar agregados. Evidentemente eso puede ser malo, así que deshacerse de ellos es bueno. ¿Cómo se acumulan esas proteínas agregadas en las células madre? Pues parece ser que los agregados de proteínas se engancha a los filamentos de actina que crecen desde el nuevo brote hacia la célula madre. Esos filamentos se ensamblan en la punta de la yema en una estructura que los autores llaman un "polarisoma", que se compone de un núcleo de proteínas junto con algunas otras (las forminas) implicadas en la polimerización de la actina. También se requiere una proteína denominada Sir2, también llamada sirtuina, que es una deacetilasa retardante del envejecimiento. Sir2 es conocida por su papel en el alargamiento de la vida media de un ser vivo, no sólo en las levaduras, también en gusanos, peces y mamíferos. Ahora se ha descubierto que Sir2 está involucrada en los procesos en los que interviene la actina, y por lo tanto en la formación de polarisoma. Es un poco más complicado de lo que aquí se describe así que para una visión más detallada, es aconsejable leer el artículo de Leonard Guarente.

El polarisoma en una yema de levadura que se está formando. Los filamentos de actina crecen desde el polarisoma y transportan los agregados proteicos hacia la célula madre (fuente).

Echemos un vistazo en un contexto algo más amplio. No se trata tan sólo de mandar la ropa sucia a la madre. Una consecuencia de la asimetría durante la gemación es que, yema tras yema, la célula madre retiene su integridad corporal, mientras que la misma se pierde si la célula se divide por fisión binaria. En las levaduras, una célula madre puede gemar entre 15 a 30 veces antes de dejar de funcionar. ¿Cómo lo sabemos? Contando pacientemente bajo el microscopio el número de veces que una célula da lugar a yemas, y usando un micromanipulador para retirar las células hijas cada vez que estas se separan de la célula madre. Así hasta que la célula madre ya no produce más yemas. ¡Imagínese separar durante 30 ocasiones a las nuevas células nacientes de la célula madre! (Esto parece ser que fue realizado por primera vez en 1950 por A.A. Barton, que a la sazón trabajaba para una compañía cervecera británica). A este fenómeno se le conoce por senescencia, y puede visualizarse por la aparición de arrugas y el aumento de tamaño de la Gran Dama. Las nuevas células inician el proceso de nuevo, y cada una de ellas será una célula madre por su cuenta. Sin embargo, se había observado que las nuevas células nacidas de "madres viejas" envejecían antes y eran cada vez menos competentes para gemar. No es de sorprender que las levaduras sean las favoritas para los estudios de polarización celular y su posible papel en la senescencia. Muchos artículos se han escrito sobre el tema.

Microfotografía de levaduras gemando. Los "botones" que pueden observarse en la levadura central son las cicatrices producidas por anteriores procesos de gemación. La expresión "Hi, bud!" significa "¡Hey colega!" y es una pequeña broma porque "bud" también significa "yema" (fuente).

Una de las conexiones entre la gemación de las levaduras y el envejecimiento se basa en una vieja teoría de hace más de 120 años propuesta por August Weismann. Él postuló que el envejecimiento evolucionó a partir de la necesidad de separar las células germinales de las células somáticas. Las células germinales deben de ser protegidas de cualquier daño; así que las células somáticas lo "cargan a sus espaldas". Una de las razones aducidas es que deben dedicarse recursos adicionales sobre las células germinales para garantizar su estabilidad genética. Las células somáticas, en cambio, no tienen esos mecanismos y por lo tanto acumulan los daños.

(A) Fotografía de un cultivo en crecimiento exponencial de levaduras en el que puede compararse el tamaño y la morfología de las células jovenes y las viejas. (B)Determinación de la edad celular. Usando técnicas de micromanipulación se cuenta el número de ciclos de gemación que cada grupo de 50 células "vírgenes" realiza hasta que se paran y no hacen más divisiones celulares. Nótese como la viabilidad va decreciendo progresivamente. (C) La célula M es una célula madre terminal después de 15 ciclos celulares. La célula D14 es una célula hija (daugther) pero no ha conseguido separarse totalmente de la madre. La célula D14-1 es una "nieta" pero ni siquiera ha comenzado su ciclo. La célula D15 también está detenida en su ciclo y no podrá separarse (fuente).

Esta es una manera de pensar en la división celular asimétrica. Formalmente, la celulas madre actúa como una célula somática que produce múltiples células germinales, las yemas. Cada una, cuando crezca, se conviertirá en una célula madre con total potencial reproductivo, capaz de producir un conjunto completo de yemas por su cuenta. Durante la gemación, la joven yema evita el daño celular que representan los agregados de proteínas, y burlando así, ese aspecto del envejecimiento celular.

Si la división celular asimétrica puede conseguir dicha protección de la línea germinal, ¿por qué no puede hacer eso cualquier célula? La cuestión no es muy relevante para las células somáticas de los organismos multicelulares, ya que no están involucrados en la propagación de la línea germinal (a menos que el investigador coja sus núcleos y los introduzca en un óvulo). Pero, ¿cómo es que los microbios unicelulares, no han adoptado la estrategia de la gemación? Esa es una pregunta para contestar en otro momento.

Dado que la levadura es el más conocido de todos los organismos eucariotas, lo que permite infinitas formas de manipulación genética, no es de extrañar que se haya convertido en un modelo para el estudio del envejecimiento. Y yo que pensaba que yo sería un buen tema para investigar lo que ocurre en la vejez!

Moselio Schaechter, autor de esta entrada

Addendum: Un comentarista llamado Qetzal dejó un comentario sobre un fenómeno similar se en bacterias. Cuando E. coli se divide, el polo "viejo" acumula chaperonas involucradas en la agregación de (presuntas) proteínas dañadas. Al cabo del tiempo, las células "viejas" pierden su capacidad reproductiva. Algo similar ocurre en Caulobacter crescentus. Así, las bacteria también puede utilizar la estrategia de la segregación de las proteínas dañadas en el interior de las células envejecidas, en beneficio de la población en su conjunto.

The primary transcriptome of the major human pathogen Helicobacter pylori

The primary transcriptome of the major human pathogen Helicobacter pylori

Nature 464, 250-255 (11 March 2010) | doi:10.1038/nature08756; Received 6 August 2009; Accepted 14 December 2009; Published online 17 February 2010

Cynthia M. Sharma¹, Steve Hoffmann², Fabien Darfeuille^3,4, Jérémy Reignier^3,4, Sven Findeiß², Alexandra Sittka¹, Sandrine Chabas^3,4, Kristin Reiche⁵, Jörg Hackermüller⁵, Richard Reinhardt⁶, Peter F. Stadler^2,5,7,8,9 & Jörg Vogel^1,10

1. Max Planck Institute for Infection Biology, RNA Biology Group, D-10117 Berlin, Germany
2. University of Leipzig, Department of Computer Science & Interdisciplinary Centre for Bioinformatics, D-04107 Leipzig, Germany
3. INSERM U869 and,
4. Université de Bordeaux, F-33076 Bordeaux Cedex, France
5. Fraunhofer Institute for Cell Therapy and Immunology, RNomics Group, D-04103 Leipzig, Germany
6. Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany
7. Max Planck Institute for the Mathematics in Sciences, D-04103 Leipzig, Germany
8. University of Vienna, Institute for Theoretical Chemistry, A-1090 Vienna, Austria
9. The Santa Fe Institute, Santa Fe, 87501 New Mexico, USA
10. University of Würzburg, Institute for Molecular Infection Biology, D-97080 Würzburg, Germany

Correspondence to: Jörg Vogel^1,10 Correspondence and requests for materials should be addressed to J.V. (Email: joerg.vogel@uni-wuerzburg.de).

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Abstract

Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent human pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5′ end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of ~60 small RNAs including the ϵ-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.

Structure, Function, and Evolution of the Thiomonas spp. Genome.

Structure, Function, and Evolution of the Thiomonas spp. Genome.: "

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Structure, Function, and Evolution of the Thiomonas spp. Genome.

PLoS Genet. 2010 Feb;6(2):e1000859

Authors: Arsène-Ploetze F, Koechler S, Marchal M, Coppée JY, Chandler M, Bonnefoy V, Brochier-Armanet C, Barakat M, Barbe V, Battaglia-Brunet F, Bruneel O, Bryan CG, Cleiss-Arnold J, Cruveiller S, Erhardt M, Heinrich-Salmeron A, Hommais F, Joulian C, Krin E, Lieutaud A, Lièvremont D, Michel C, Muller D, Ortet P, Proux C, Siguier P, Roche D, Rouy Z, Salvignol G, Slyemi D, Talla E, Weiss S, Weissenbach J, Médigue C, Bertin PN

Bacteria of the Thiomonas genus are ubiquitous in extreme environments, such as arsenic-rich acid mine drainage (AMD). The genome of one of these strains, Thiomonas sp. 3As, was sequenced, annotated, and examined, revealing specific adaptations allowing this bacterium to survive and grow in its highly toxic environment. In order to explore genomic diversity as well as genetic evolution in Thiomonas spp., a comparative genomic hybridization (CGH) approach was used on eight different strains of the Thiomonas genus, including five strains of the same species. Our results suggest that the Thiomonas genome has evolved through the gain or loss of genomic islands and that this evolution is influenced by the specific environmental conditions in which the strains live.

PMID: 20195515 [PubMed - in process]

"

Genome update: the 1000th genome – a cautionary tale

Microbiology 156 (2010), 603-608; DOI  10.1099/mic.0.038257

A human gut microbial gene catalogue established by metagenomic sequencing

Nature 464, 59-65 (4 March 2010) | doi:10.1038/nature08821; Received 14 August 2009; Accepted 23 December 2009

Bacterial actin MreB assembles in complex with cell shape protein RodZ.

Bacterial actin MreB assembles in complex with cell shape protein RodZ.: "

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Bacterial actin MreB assembles in complex with cell shape protein RodZ.

EMBO J. 2010 Feb 18;

Authors: van den Ent F, Johnson CM, Persons L, de Boer P, Löwe J

Bacterial actin homologue MreB is required for cell shape maintenance in most non-spherical bacteria, where it assembles into helical structures just underneath the cytoplasmic membrane. Proper assembly of the actin cytoskeleton requires RodZ, a conserved, bitopic membrane protein that colocalises to MreB and is essential for cell shape determination. Here, we present the first crystal structure of bacterial actin engaged with a natural partner and provide a clear functional significance of the interaction. We show that the cytoplasmic helix-turn-helix motif of Thermotoga maritima RodZ directly interacts with monomeric as well as filamentous MreB and present the crystal structure of the complex. In vitro and in vivo analyses of mutant T. maritima and Escherichia coli RodZ validate the structure and reveal the importance of the MreB-RodZ interaction in the ability of cells to propagate as rods. Furthermore, the results elucidate how the bacterial actin cytoskeleton might be anchored to the membrane to help constrain peptidoglycan synthesis in the periplasm.

PMID: 20168300 [PubMed - as supplied by publisher]

"

Organic-walled microfossils in 3.2-billion-year-old shallow-marine siliciclastic deposits.

 Although the notion of an early origin and diversification of life on Earth during the Archaean eon has received
increasing support in geochemical, sedimentological and palaeontological evidence, ambiguities and
controversies persist regarding the biogenicity and syngeneity of the record older than Late Archaean.

Non-biological processes are known to produce morphologies similar to some microfossils, and hydrothermal fluids have the potential to produce abiotic organic compounds with depleted carbon isotope values, making it difficult to establish unambiguous traces of life. Here we report the discovery of a population of large (up to about 300 μm in diameter) carbonaceous spheroidal microstructures in Mesoarchaean shales and siltstones of the Moodies Group, South Africa, the Earth’s oldest siliciclastic alluvial to tidal-estuarine deposits. These microstructures are interpreted as organic-walled microfossils on the basis of petrographic and geochemical evidence for their endogenicity and syngeneity, their carbonaceous composition, cellular morphology and ultrastructure, occurrence in populations, taphonomic features of soft wall deformation, and the geological context plausible for life, as well as a lack of abiotic explanation falsifying a biological origin. These are the oldest and largest Archaean organic-walled spheroidal microfossils reported so far. Our observations suggest that relatively large microorganisms cohabited with earlier reported benthic microbial matsin the photic zone of marginal marine siliciclastic environments 3.2 billion years ago.

Javaux, Emmanuelle J., Craig P. Marshall, y Andrey Bekker. 2010. Organic-walled microfossils in 3.2-billion-year-old shallow-marine siliciclastic deposits. Nature 463, no. 7283 (Febrero 18): 934-938. 

doi:10.1038/nature08793. http://dx.doi.org/10.1038/nature08793. 

Secuenciado el genoma de un hombre de hace 4000 años

Ancient human genome sequence of an extinct Palaeo-Eskimo.

We report here the genome sequence of an ancient human. Obtained from ~4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20×, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit

Nature 463, 757-762 (11 February 2010) | doi:10.1038/nature08835; Received 30 November 2009; Accepted 18 January 2010

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